Cells and cytokines in immunotherapy and gene therapy for cancer

Critical Reviews in Oncogenesis

Volumn 10, Issue 1-2, 1999, Pages 83-127

  Pawelec, Graham ^a,h   Rees, Robert C ^b   Kiessling, Rolf ^c   Madrigal, Alejandro ^d   Dodi, Anthony ^d   Baxevanis, Constantine ^e   Gambacorti Passerini, Carlo ^f   Masucci, Guiseppe ^c   Zeuthen, Jesper ^g  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b NOTTINGHAM TRENT UNIVERSITY   (United Kingdom)

^c KAROLINSKA INSTITUTE   (Sweden)

^d ROYAL FREE HOSPITAL   (United Kingdom)

^e Hellenic Anticancer Institute   (Greece)

^f Ist Natl Per lo Stud E la Cura D   (Italy)

^g DANISH CANCER SOCIETY RESEARCH CENTER   (Denmark)

^h UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

Author keywords

Active immunotherapy; Adoptive immunotherapy; Cancer therapy; Cytokines; Gene therapy; Immunosurveillance; Immunotherapy; T cell mediated immunity; Tumor antigen; Tumor rejection

Indexed keywords

ALPHA INTERFERON; ANTINEOPLASTIC AGENT; CANCER VACCINE; CISPLATIN; CYTOKINE RECEPTOR; FLUOROURACIL; FOLINIC ACID; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HLA ANTIGEN; INTERLEUKIN 2; INTERLEUKIN 4; MAJOR HISTOCOMPATIBILITY ANTIGEN; MELANOMA VACCINE; SYNTHETIC PEPTIDE; THYMOPENTIN; TUMOR ANTIGEN;

ADOPTIVE IMMUNOTHERAPY; ANIMAL MODEL; BREAST CANCER; CANCER IMMUNOLOGY; CANCER IMMUNOTHERAPY; CANCER THERAPY; CLINICAL TRIAL; COLORECTAL CANCER; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DENDRITIC CELL; DOUBLE BLIND PROCEDURE; GENE THERAPY; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; KIDNEY CARCINOMA; LUNG CANCER; MAJOR CLINICAL STUDY; MELANOMA; METASTASIS; MULTICENTER STUDY; NONHUMAN; PHASE 1 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; PROGNOSIS; PROSTATE CANCER; RANDOMIZED CONTROLLED TRIAL; REVIEW; SUBCUTANEOUS DRUG ADMINISTRATION;

EID: 0032951479     PISSN: 08939675     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (382)

1. Aaltomaa, S. et al.: Lymphocyte infiltrates as a prognostic variable in female breast cancer. Eur. J. Cancer, 28A: 859-864 (1992).
2. Abdel-Wahab, Z. et al.: Human dendritic cells, pulsed with either melanoma tumor cell lysates or the gp100 peptide (280-288), induce pairs of T-cell cultures with similar phenotype and lytic activity. Cell. Immunol., 186: 63-74 (1998).
3. + T-cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations. Cell. Immunol., 182: 137-151 (1997).
4. Aebersold, P. et al.: Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes - association with clinical response. J. Natl. Cancer Inst., 83:932-937 (1991).
5. Alexander-Miller, M. A., G. R. Leggatt, and J. A. Berzofsky: Selective expansion of high-or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. Proc. Natl. Acad. Sci. U.S.A., 93: 4102-4107 (1996).
6. Alijagic, S. et al.: Dendritic cells generated from peripheral blood transfected with human tyrosinase induce specific T-cell activation. Eur. J. Immunol., 25: 3100-3107 (1995).
7. Allione, A. et al.: Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene or admixed with conventional adjuvants. Cancer Res., 54:6022-6026 (1994).
8. Allison, J. et al.: The threshold for autoimmune cell killing is influenced by B7-1. Eur. J. Immunol., 28: 949-960 (1998).
9. Anderson, D. O. et al.: Tumorigenicity and immunogenicity of genetically-modified RenCa. Cancer Gene. Ther., 2: 622-628 (1995).
10. Aoki, T. et al.: Expression of murine interleukin-7 in a murine glioma cell line results in reduced tumorigenicity in vivo. Proc. Natl. Acad. Sci. U.S.A., 89: 3850-3854 (1992).
11. Arienti, F. et al.: Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2. Cancer Immunol. Immunother., 36: 315-322 (1993).
12. Arienti, F. et al.: Limited antitumor T-cell response in melanoma patients vaccinated with interleukin-2 gene-transduced allogeneic melanoma cells. Hum. Gene. Ther., 7: 1955-1963 (1996).
13. Armstrong, T. D. et al.: Major histocompatibility complex class II-transfected tumor cells present endogenous antigen and are potent inducers of tumor-specific immunity. Proc. Natl. Acad. Sci. U.S.A., 94: 6886-6891 (1997).
14. Armstrong, T. D., B. A. Pulaski, and S. Ostrand-Rosenberg: Tumor antigen presentation: changing the rules. Cancer Immunol. Immunother., 46: 70-74 (1998).
15. Bain, C. et al.: Correlation between clinical response to interleukin 2 and HLA phenotypes in patients with metastatic renal cell carcinoma. Br. J. Cancer, 75: 283-286 (1997).
16. Bakker, A. B. H. et al.: Generation of antimelanoma cytotoxic T lymphocytes from healthy donors after presentation of melanoma-associated antigen-denved epitopes by dendritic cells in vitro. Cancer Res., 55: 5330-5334 (1995).
17. Bakker, A. B. H. et al.: Analogues of CTL epitopes with improved MHC class-I binding capacity elicit anti-melanoma CTL recognizing the wild-type epitope. Int. J. Cancer, 70: 302-309 (1997).
18. Bannerji, R. et al.: The role of IL-2 secreted fro genetically modified tumor cells in the establishment of antitumor immunity. J. Immunol., 152: 2324-2332 (1994).
19. Barba, D. et al.: Development of antitumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc. Natl. Acad. Sci. U.S.A., 91: 4348-1352 (1994).
20. Barth, A. et al.: Polyvalent melanoma cell vaccine induces delayed-type hypersensitivity and in vitro cellular immune response. Cancer Res., 54: 3342-3345 (1994).
21. Baskar, S. et al.: Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated major histocompatibility complex class-II molecules. Proc. Natl. Acad. Sci. U.S.A., 90: 5687-5690 (1993).
22. + tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice. J. Exp. Med., 181: 619-629 (1995).
23. Baskar, S. et al.: Rejection of MHC class II-transfected tumor cells requires induction of tumor-encoded B7-1 and/or B7-2 costimulatory molecules. J. Immunol., 156: 3821-3827 (1996).
24. Bass, K. K. and M. J. Mastrangelo: Immunopotentiation with low-dose cyclophosphamide in the active specific immunotherapy of cancer. Cancer Immunol. Immunother., 47: 1-12 (1998).
25. Baxevanis, C. N. et al.: Interleukin 1-beta synergises with interleukin-2 in the outgrowth of autologous tumour-reactive CD8+ effectors. Br. J. Cancer, 70: 625-630 (1994).
26. Baxevanis, C. N. et al.: Granulocyte-macrophage colony-stimulating factor improves immunological parameters in patients with refractory solid tumours receiving second-line chemotherapy: Correlation with clinical responses. Eur. J. Cancer, 33: 1202-1208 (1997).
27. Baxevanis, C. N. et al.: Mistletoe lectin I-induced effects on human cytotoxic lymphocytes. I. Synergism with IL-2 in the induction of enhanced LAK cytotoxicity. Immunopharmacol. Immunotoxicol., 20: 355-372 (1998).
28. Belldegrun, A. et al.: Natural immune reactivity-associated therapeutic response in patients with metastatic renal cell carcinoma receiving tumor-infiltrating lymphocytes and interleukin-2-based therapy. J. Immunother., 19: 149-161 (1996).
29. Belli, F. et al.: Active immunization of metastatic melanoma patients with interleukin-2-transduced allogeneic melanoma cells: evaluation of efficacy and tolerability. Cancer Immunol. Immunother., 44: 197-203 (1997).
30. Bellone, M. et al.: Rejection of a nonimmunogenic melanoma by vaccination with natural melanoma peptides on engineered antigen-presenting cells. J. Immunol., 158: 783-789 (1997).
31. Berd, D. et al.: Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatment after resection of nodal metastases. J. Clin. Oncol., 15: 2359-2370 (1997).
32. Berglund, P. et al.: Enhancing immune responses using suicidal DNA vaccines. Natl. Biotechnol., 16: 562-565 (1998).
33. Berman, R. M. et al.: Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice. J. Immunol., 157: 231-238 (1996).
34. Bettinotti, M. P. et al.: Stringent allele/epitope requirements for MART-1/Melan A immunodominance: implications for peptide-based immunotherapy. J. Immunol., 161: 877-889 (1998).
35. Bianchi, R. et al.: IL-12 is both required and sufficient for initiating T-cell reactivity to a class I-restricted tumor peptide (P815AB) following transfer of P815AB-pulsed dendritic cells. J. Immunol., 157: 1589-1597 (1996).
36. Bloemena, E. et al.: Delayed-type hypersensitivity reactions to tumor-associated antigens in colon carcinoma patients immunized with an autologous tumor cell/bacillus-calmetteguerin vaccine. Cancer Res., 53: 456-459 (1993).
37. Boczkowski, D. et al.: Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J. Exp. Med., 184: 465-472 (1996).
38. Bugeon, L. et al.: Similar levels of granzyme-A and perforin messenger RNA expression in rejected and tolerated heart allografts in donor-specific tolerance in rats. Transplantation, 56: 405-408 (1993).
39. Bukowski, R. M. et al.: Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin-2 in human metastatic renal cell carcinoma. Cancer Res., 51: 4199-4205 (1991).
40. Bukowski, R. M. et al.: Phase II trial of interleukin-2 and interferon-alpha in patients with renal cell carcinoma: clinical results and immunologic correlates of response. J. Immunother., 20: 301-311 (1997).
41. Burno, D. K. et al.: Transfection of a murine fibrosarcoma with intercellular adhesion molecule-1 enhances the response to adoptive immunotherapy. Surgery, 118: 237-244 (1995).
42. Buschle, M. et al.: Transloading of tumor antigen-derived peptides into antigen-presenting cells. Proc. Natl. Acad. Sci. US.A., 94: 3256-3261 (1997).
43. Buzio, C. et al.: Effectiveness of very low doses of immunotherapy in advanced renal cell cancer. Br. J. Cancer, 76: 541-544 (1997).
44. Bystryn, J. C. et al.: Relationship between immune response to melanoma vaccine immunization and clinical outcome in stage-II malignant melanoma. Cancer, 69: 1157-1164 (1992).
45. Cavallo, F. et al.: Coexpression of B7-1 and ICAM-1 on tumors is required for rejection and the establishment of a memory response. Eur. J. Immunol., 25: 1154-1162 (1995).
46. Cayeux, S. et al.: Tumor cells cotransfected with interleukin-7 and B7.1 genes induce CD25 and CD28 on tumor-infiltrating T lymphocytes and are strong vaccines. Eur. J. Immunol., 25: 2325-2331 (1995).
47. Cayeux, S. et al.: Coexpression of interleukin-4 and B7.1 in murine tumor cells leads to improved tumor rejection and vaccine effect compared to single gene transfectants and a classical adjuvant. Hum. Gene. Ther., 7: 525-529 (1996).
48. Cella, M. et al.: Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature, 388: 782-787 (1997).
49. Celluzi, C. M. and L. D. Falo: Physical interaction between dendritic cells and tumor cells results in an immunogen that induces protective and therapeutic tumor rejection. J. Immunol., 160: 3081-3085 (1998).
50. Celluzzi, C. M. et al.: Peptide-pulsed dendritic cells induce antigen-specific, CTL-mediated protective tumor immunity. J. Exp. Med., 183: 283-287 (1996).
51. Chakraborty, N. G. et al.: Immunization with a tumor-cell-lysate-loaded autologous-antigen-presentmg-cell-based vaccine in melanoma. Cancer Immunol. Immunother., 47: 58-64 (1998).
52. Chang, A. E. et al.: A phase II trial of interleukin-2 and interferon-alpha in the treatment of metastatic colorectal carcinoma. J. Immunother., 18: 253-262 (1995).
53. Chang, A. E. et al.: Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2. J. Clin. Oncol., 15: 796-807 (1997).
54. Chaturvedi, P. et al.: Peptide analogs with different affinities for MHC alter the cytokine profile of T helper cells. Int. Immunol., 8: 745-755 (1996).
55. Chen, L. P. et al.: Costimulation of antitumor immunity by the B7 counter-receptor for the lymphocyte-T molecules CD28 and CTLA-4. Cell. 71: 1093-1102 (1992).
56. Chen, L. P. et al.: B7-1 CD80-transduced tumor cells elicit better systemic immunity than wild-type tumor cells admixed with Corynebacterium parvum. Cancer Res., 54: 5420-5423 (1994a).
57. Chen, L. P. et al.: Tumor immunogenicity determines the effect of B7 costimulation on T-cell-mediated tumor immunity. J. Exp. Med., 179: 523-532 (1994b).
58. Chen, P. W. and H. N. Ananthaswamy: Rejection of K1735 murine melanoma in syngeneic hosts requires expression of MHC class-I antigens and either class-II antigens or IL-2. J. Immunol., 151: 244-255 (1993).
59. + T lymphocytes by murine melanoma cells transfected with major histocompatibility complex class II genes. J. Leukocyte Biol., 56: 469-474 (1994).
60. Chong, H. et al.: Expression of costimulatory molecules by tumor cells decreases tumorigenicity but may also reduce systemic antitumor immunity. Hum. Gene Ther., 7: 1771-1779 (1996).
61. Chow, M. and H. Rubin: Irreversibility of cellular aging and neoplastic transformation: a clonal analysis. Proc. Natl. Acad. Sci. U.S.A., 93: 9793-9798 (1996).
62. Ciernik, I. F., J. A. Berzofsky, and D. P. Carbone: Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T-cell epitopes J. Immunol., 156, 2369-2375 (1996).
63. Clary, B. M. et al.: Active immunotherapy of pancreatic cancer with tumor cells genetically engineered to secrete multiple cytokines. Surgery, 120: 174-181 (1996)
64. Clemente, C. G. et al.: Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer, 77: 1303-1310 (1996)
65. Clements, V. K. et al.: Invariant chain alters the malignant phenotype of MHC class-II tumor cells. J. Immunol., 149: 2391-2396 (1992).
66. Cochlovius, B. et al.: Stable expression of a retrovirally transferred adhesion molecule in a human melanoma-specific cytgotoxic T lymphocyte clone. Cancer Immunol. Immunother., 46: 61-66 (1998).
67. Condon, C. et al.: DNA-based immunization by in vivo transfection of dendritic cells. Nature Med., 2: 1122-1128 (1996).
68. Consalvo, M. et al.: 5-fluorocytosine-induced eradication of murine adenosarcoma engineered to express the cytosine deaminase suicide gene requires host immune competence and leaves an efficient memory. J. Immunol., 154: 5302-5312 (1995).
69. Coughlin, C. M. et al.: B7-1 and interleukin-12 synergistically induce effective antitumor immunity. Cancer Res., 55: 4980-4987 (1995).
70. Crowley, N. J., C. E. Vervaert, and H. F. Seigler: Human xenograft-nude mouse model of adoptive immunotherapy with human melanoma-specific cytotoxic T-Cells. Cancer Res., 52: 394-399 (1992).
71. Curti, B. D. et al.: Influence of interleukin-2 regimens on circulating populations of lymphocytes after adoptive transfer of anti-CD3-stimulated T cells: results from a phase I trial in cancer patients. J. Immunother., 19: 296-308 (1996).
72. + T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer. J. Clin. Oncol., 16: 2752-2760 (1998).
73. De Bruijn, M. L. H. et al.: Immunization with human papillomavirus type 16 (HPV 16) oncoprotein-loaded dendritic cells as well as protein adjuvant induced MHC class I-restricted protection to HPV-16-induced tumor cells. Cancer Res., 58: 724-731 (1998).
74. Deehan, D. J. et al.: In vivo cytokine production and recombinant interleukin-2 immunotherapy: an insight into the possible mechanisms underlying clinical responses. Br. J. Cancer, 69: 1130-1135 (1994).
75. De Wit, D. et al.: IL-12 stimulation but not B7 expression increases melanoma killing by patient cytotoxic T lymphocytes (CTL). Clin. Exp. Immunol., 105: 353-359 (1996).
76. Diederichsen, A. C. P. et al.: Flow cytometric investigation of immune-response-related surface molecules on human colorectal cancers. Int. J. Cancer, 79: 283-287 (1998a).
77. Diederichsen, A. C. P. et al.: Immunisation of colorectal cancer patients with autologous tumor cells. Oncol. Rep., 5: 823-844 (1998b).
78. Dietrich, P. Y. et al.: TCR analysis reveals significant repertoire selection during in vitro lymphocyte culture. Int. Immunol., 9: 1073-1083 (1997).
79. Dillman, R. O. et al.: Continuous interleukin-2 and tumor-infiltrating lymphocytes as treatment of advanced melanoma - a National Biotherapy Study Group trial. Cancer, 68: 1-8 (1991).
80. Dillman, R. O. et al.: Clinical experience with autologous tumor cell lines for patient-specific vaccine therapy in metastatic melanoma. Cancer Biother. Radiopharm., 13: 165-176 (1998).
81. Dilloo, D. et al.: Combined chemokine and cytokine gene transfer enhances antitumor immunity. Nature Med., 2: 1090-1095 (1996).
82. Disis, M. L. et al.: Peptide-based, but not whole protein, vaccines elicit immunity to HER-2/neu, an oncogenic self-protein. J. Immunol., 156: 3151-3158 (1996).
83. Dohring, C. et al.: T-helper and accessory-cell-independent cytotoxic responses to human tumor cells transfected with a B7 retroviral vector. Int. J. Cancer, 57: 754-759 (1994).
84. Douvdevani, A. et al.: Reduced tumorigenicity of fibrosarcomas which constitutively generate IL-1-alpha either spontaneously or following IL-1-alpha gene transfer. Int. J. Cancer, 51: 822-830 (1992).
85. Dunussi Joannopoulos, K. et al.: Irradiated B7-1 transduced primary acute myelogenous leukemia (AML) cells can be used as therapeutic vaccines in murine AML. Blood, 87: 2938-2946 (1996).
86. Dutcher, J. P. et al.: Interelukin-2-based therapy for metastatic renal cell cancer: the Cytokine Working Group exprience, 1989-1997. Cancer J. Sci. Am., (3 Suppl.) 1: S73-S78 (1998).
87. Economou, J. S. et al.: In vivo trafficking of adoptively transferred interleukin-2 expanded tumor-infiltrating lymphocytes and peripheral blood lymphocytes - results of a double gene marking trial. J. Clin. Invest., 97: 515-521 (1996).
88. Eibl, B. et al.: Dendritic cells generated from blood precursors of chronic myelogenous leukemia patients carry the Philadelphia translocation and can induce a CML-specific primary cytotoxic T-cell response. Gene Chromosome Cancer, 20: 215-223 (1997).
89. Ellem, K. A. O. et al.: A case report: immune responses and clinical course of the first human use of granulocyte/ macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy. Cancer Immunol. Immunother., 44: 10-20 (1997).
90. Elsasser-Beile, U. et al.: Correlation of clinical and immunological parameters of metastatic renal cell carcinoma patients undergoing therapy with interleukin-2, interferon-alpha and retinoic acid. Anticancer Res., 18: 1883-1890 (1998).
91. Engering, A. J. et al.: The mannose receptor functions as a high capacity and broad specificity antigen receptor in human dendritic cells. Eur. J. Immunol., 27: 2417-2425 (1997).
92. Escudier, B. et al.: Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated natural killer cells: improvement of clinical responses in metastatic renal cell carcinoma patients previously treated with IL-2. Eur. J. Cancer, 30A: 1078-1083 (1994).
93. Evans, R. et al.: IL-15 mediates antitumor effects after cyclophosphamide injection of tumor-bearing mice and enhances adoptive immunotherapy: the potential role of NK cell subpopulations. Cell Immunol., 179: 66-73 (1997).
94. Fallarino, F. et al.: Endogenous IL-12 is necessary for rejection of P815 tumor variants in vivo. J. Immunol., 156: 1095-1100 (1996).
95. Farace, F. et al.: Metastatic renal-cell carcinoma patients treated with interleukin-2 or interleukin-2 plus interferon-gamma: immunological monitoring. Int. J. Cancer, 57: 814-821 (1994).
96. Fearon, E. R. et al.: Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell, 60: 397-403 (1990).
97. Fenton, R. G. et al.: A phase I randomized study of subcutaneous adjuvant IL-2 in combination with an autologous tumor vaccine in patients with advanced renal cell carcinoma. J. Immunother., 19: 364-374 (1996).
98. Fernandez, N. et al.: Active specific T-cell-based immunotherapy for cancer: nucleic acids, peptides, whole native proteins, recombinant viruses, with dendritic cell adjuvants or whole tumor cell-based vaccines. Principles and future prospects. Cytokines. Cell. Mol. Ther., 4: 53-65 (1998).
99. + selected tumor infiltrating lymphocytes from primary tumor. J. Urol., 158: 740-745 (1997).
100. Fioretti, F. et al.: Reduced tumorigenicity and augmented leukocyte infiltration after monocyte chemotactic protein-3 (MCP-3) gene transfer: perivascular accumulation of dendritic cells in pentumoral tissue and neutrophil recruitment within the tumor. J. Immunol., 161: 342-346 (1998).
101. Flores, I. et al.: IFN-gamma and B7 as costimulators of antitumor immune responses. Int. J. Oncol., 7: 501-509 (1995).
102. Freeman, S. M. et al.: The bystander effect - tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res., 53: 5274-5283 (1993).
103. Freeman, S. M., R. Ramesh, and A. J. Marrogi: Immune system in suicide gene therapy. Lancet, 349: 2-3 (1997).
104. Gabrilovich, D. I., H. T. Cunningham, and D. P. Carbone: IL-12 and mutant p53 peptide-pulsed dendritic cells for the specific immunotherapy of cancer. J. Immunother., 19: 414-418 (1996).
105. Galligioni, E. et al.: Adjuvant immunotherapy treatment of renal carcinoma patients with autologous tumor cells and Bacillus Calmette-Guerin: five-year results of a prospective randomized study. Cancer, 77: 2560-2566 (1996).
106. Gambacorti-Passerini, C. et al.: Serum CD25 levels in patients treated with recombinant interleukin-2 and lymphokine activated killers. Correlation with immune activation and induction of immunosuppressive activity. J. Immunol. Res., 2: 19-24 (1990).
107. Gambacorti-Passerini, C. et al.: A pilot phase II trial of continuous infusion interleukin-2 followed by LAK therapy and bolus infusion IL2 in renal cancer. J. Immunother., 13: 43-48 (1993).
108. Gansbacher, B. et al.: A pilot study of immunization with HLA-A2 matched allogeneic melanoma cells that secrete interleukin-2 in patients with metastatic melanoma - Memorial Sloan-Kettering Cancer Center. Hum. Gene Ther., 3: 677-690 (1992a).
109. Gansbacher, B. et al.: A pilot study of immunization with interleukin-2 secreting allogeneic HLA-A2 matched renal cell carcinoma cells in patients with advanced renal cell carcinoma - Memorial Sloan-Kettering Cancer Center. Hum. Gene Ther., 3: 691-703 (1992b).
110. Gansbacher, B. et al.: Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-gamma in irradiated human melanoma cells. Blood, 80: 2817-2825 (1992c).
111. Garrido, F. et al.: Natural history of HLA expression during tumour development. Immunol. Today, 14: 491-499 (1993).
112. Gilligan, M. G. et al.: Adenoviral delivery of B7-1 (CD80) increases the immunogenicity of human ovarian and cervical carcinoma cells. Gene Therapy, 5: 965-974 (1998).
113. Gjertsen, M. K. et al.: Characterisation of immune responses in pancreatic carcinoma patients after mutant p21 ras peptide vaccination. Br. J. Cancer, 74: 1828-1833 (1996a).
114. Gjertsen, M. K. et al.: Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study. Int. J. Cancer, 65: 450-453 (1996b).
115. + T lymphocytes, generated by mutant p21-ras (12Val) peptide vaccination of a patient, recognize 12Val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation. Int. J. Cancer, 72: 784-790 (1997).
116. Gnjatic, S. et al.: Accumulation of the p53 protein allows recognition by human CTL of a wild-type p53 epitope presented by breast carcinomas and melanomas. J. Immunol., 160: 328-333 (1998).
117. Gold, J. E. et al.: Adoptive chemoimmunotherapy for the treatment of relapsed and refractory solid tumors using ex vivo activated memory T-cells (Autolymphocyte Therapy) and cyclophosphamide. J. Immunother., 13: 213-221 (1993).
118. Gold, P. J. et al.: Metastatic renal cell carcinoma: long-term survival after therapy with high-dose continuos-infusion interleukin-2. Cancer J. Sci. Am., (3 Suppl.) 1: S85-S91 (1998).
119. Golumbek, P. T. et al.: Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science, 254: 713-716 (1991).
120. Gong, J. L. et al.: Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nature Med., 3, 558-561 (1997).
121. Gordon, M. Y. et al.: Treatment with interferon-alpha preferentially reduces the capacity for AMPlification of granulocyte-macrophage progenitors (CFU-GM) from patients with chronic myeloid leukemia but spares normal CFU-GM. J. Clin. Invest., 102: 710-715 (1998).
122. Goydos, J. S. et al.: A phase I trial of a synthetic mucin peptide vaccine induction of specific immune reactivity in patients with adenocarcinoma. J. Surg. Res., 63: 298-304 (1996).
123. Graham, R. A. et al.: Intramuscular immunisation with MUC1 cDNA can protect C57 mice challenged with MUC1-expressing syngeneic mouse tumour cells. Int. J. Cancer, 5:664-670 (1996).
124. Greenberg, P. D.: Adoptive T-cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. Adv. Immunol., 49: 281-355 (1991).
125. Grohmann, U. et al.: A tumor-associated and self-antigen peptide presented by dendritic cells may induce T-cell anergy in vivo, but IL-12 can prevent or revert the anergic state. J. Immunol., 158: 3593-3602 (1997).
126. Habicht, A. et al.: Development of immunogenic colorectal cancer cell lines for vaccination: expression of CD80 (B7.1) is not sufficient to restore impaired primary T-cell activation in vitro. Eur. J. Cancer, 31A: 2396-2402 (1995).
127. Hakansson, A. et al.: Tumour-infiltrating lymphocytes in metastatic malignant melanoma and response to interferon alpha treatment. Br. J. Cancer, 74:670-676 (1996).
128. Hank, J. et al.: Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody together with interleukin-2 in cancer patients. Clin. Cancer Res., 1: 481-492 (1995).
129. Hanninen, E. L., H. Kirchner, and J. Atzpodien: Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients. J. Urol., 155: 19-25 (1996).
130. Haque, T. et al.: Reconstitution of EBV-specific T-cell immunity in solid organ transplant recipients. J. Immunol., 160: 6204-6209 (1998).
131. Haruta, I. et al.: Analytical study of the clinical response to two distinct adoptive immunotherapies for advanced hepatocellular carcinoma: comparison between LAK cell and CTL therapy. J. Immunother., 19: 218-223 (1996).
132. Hathorn, R. W. et al.: In vitro modulation of the invasive and metastatic potentials of human renal cell carcinoma by interleukin-2 and/or interferon-alpha gene transfer. Cancer, 74: 1904-1911 (1994).
133. + lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma. Cancer Immunol. Immunother., 34: 111-114 (1991).
134. Hermann, G. G. et al.: Recombinant interleukin-2 and lymphokine-activated killer cell treatment of advanced bladder cancer - clinical results and immunological effects. Cancer Res., 52: 726-733 (1992).
135. Hersh, E. M. et al.: Phase I study of immunotherapy of malignant melanoma by direct gene transfer. Hum. Gene Ther., 5: 1371-1384 (1994).
136. Heslop, H. E. et al.: Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nature Med., 2:551-555 (1996).
137. Hirschowitz, E. A. et al.: Adenovirus-mediated expression of melanoma antigen gp75 as immunotherapy for metastatic melanoma. Gene Therapy, 5: 975-983 (1998).
138. Hirst, W. J. R. et al.: Enhanced immune costimulatory activity of primary acute myeloid leukemia blasts after retrovirus-mediated gene transfer of B7.1. Gene Therapy, 4: 691-699 (1997).
139. Hobarth, K. et al.: Circulating immune markers in advanced renal cell carcinoma during immunotherapy with interferon gamma. Urol. Res., 24: 101-106 (1996).
140. + T-cell-dependent tumor rejection. J. Exp. Med., 174: 1291-1298 (1991).
141. Hock, H. et al.: Vaccinations with tumor cells genetically engineered to produce different cytokines - effectivity not supenor to a classical adjuvant. Cancer Res., 53: 714-716 (1993).
142. Hock, R. A. et al.: Human class II major histocompatibility complex gene transfer into murine neuroblastoma leads to loss of tumorigenicity, immunity against subsequent tumor challenge, and elimination of microscopic preestablished tumors. J. Immunother., 17: 12-18 (1995).
143. Hodge, J. W. et al.: Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res., 54: 5552-5555 (1994).
144. Hodge, J. W. et al.: Admixture of a recombinant vaccinia virus containing the gene for the costimulatory molecule B7 and a recombinant vaccinia virus containing a tumor-associated antigen gene results in enhanced specific T-cell responses and antitumor immunity. Cancer Res., 55: 3598-3603 (1995).
145. Hofmockel, G. et al.: Immunochemotherapy for metastatic renal cell carcinoma using a regimen of interleukin-2, interferon-alpha, and 5-fluorouracil. J. Urol., 156: 18-21 (1996).
146. Hoon, D. S. B. et al.: Melanoma patients immunized with melanoma cell vaccine induce antibody responses to recombinant MAGE-1 antigen. J. Immunol., 154: 730-737 (1995).
147. Hsu, F. J. et al.: Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med., 2: 52-58 (1996).
148. Hsueh, E. C. et al.: Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine. J. Clin. Oncol., 16: 2913-2920 (1998).
149. Hui, K., F. Grosveld, and H. Festenstein: Rejection of transplantable AKR leukemia cells following MHC DNA-mediated cell transformation. Nature, 311: 750 (1984).
150. Hunt, J. D. et al.: Transfer and expression of the human interleukin-4 gene in carcinoma and stromal cell lines derived from lung cancer patients. J. Immunother., 14: 314-321 (1993).
151. Hwu, P. et al.: Functional and molecular characterization of tumor-infiltrating lymphocytes transduced with tumor necrosis factor-alpha cDNA for the gene therapy of cancer in humans. J. Immunol., 150: 4104-4115 (1993).
152. + ThO cell clones, isolated from a metastatic lymph node of a melanoma patient, possess cytolytic function. Cancer Immunol. Immunother., 41: 210-216 (1995).
153. Imro, M. A. et al.: Human melanoma cells transfected with the B7-2 costimulatory molecule induce tumor-specific CD8(+) cytotoxic T lymphocytes in vitro. Hum. Gene Ther., 9: 1335-1344 (1998).
154. Irvine, K. R. et al.: Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. J. Immunol., 156: 238-245 (1996).
155. Itoh, Y. et al.: Human tumor-infiltrating lymphocytes transfected with tumor necrosis factor gene could augment cytotoxicity to autologous tumor cells. Jpn. J. Cancer Res., 82: 1203-1206 (1991).
156. Itoh, Y. et al.: Characterization of tumor necrosis factor gene transduced tumor-infiltrating lymphocytes from ascitic fluid of cancer patients: analysis of cytolytic activity, growth rate, adhesion molecule expression, and cytokine production. Cancer Immunol. Immunother., 40: 95-102 (1995).
157. Jager, E. et al.: Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens. Int. J. Cancer, 66: 162-169 (1996a).
158. Jaer, E. et al.: Granulocyte macrophage colony stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int. J. Cancer, 67:54-62 (1996b).
159. + cytolytic T lymphocytes. J. Exp. Med., 183: 791-800 (1996).
160. Jung, D. et al.: Strong immunogenic potential of a B7 retroviral expression vector: generation of HLA-B7-restricted CTL response against selectable marker genes. Hum. Gene Ther., 9: 53-62 (1998).
161. Kang, X. Q. et al.: Induction of melanoma reactive T cells by stimulator cells expressing melanoma epitope-major histocompatibility complex class I fusion proteins. Cancer Res., 57: 202-205 (1997).
162. Katsanis, E. et al.: Interleukin-2 gene transfer into murine neuroblastoma decreases tumongenicity and enhances systemic immunity causing regression of preestablished retroperitoneal tumors. J. Immunother., 15: 81-90 (1994).
163. Katsumi, A. et al.: Humoral and cellular immunity to an encoded protein induced by direct DNA injection. Hum. Gene Ther., 5: 1335-1339 (1994).
164. Kaufmann, A. M. et al.: Expression of CD80 enhances immunogenicity of cervical carcinoma cells in vitro. Cell. Immunol., 169: 246-251 (1996).
165. Keating, P. J. et al.: Frequency of downregulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression. Br. J. Cancer, 72: 405-411 (1995).
166. Kedar, E. et al.: Delivery of cytokines by liposomes. 2. Interleukin-2 encapsulated in long-circulating sterically stabilized liposomes: immunomodulatory and antitumor activity in mice. J. Immunother., 16: 115-124 (1994).
167. Keilholz, U. et al.: Recombinant interelukin 2-based treatments for advanced melanoma: the experience of the European organization for research and treatment of cancer melanoma cooperative group. Cancer J. Sci. Am., (3 Suppl.) 1: S22-S28 (1998a).
168. Keilholz, U. et al.: Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients. J. Clin. Oncol., 16: 2921-2929 (1998b).
169. Kelly, S. A. et al.: Enhancement of metastatic potential by gamma-interferon. Cancer Res., 51: 4020-4027 (1991).
170. Khazaie, K. et al.: Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection. Proc. Natl. Acad. Sci. U.S.A., 91: 7430-7434 (1994).
171. Kim, C. J. et al.: Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma. J. Immunother., 19: 50-58 (1996).
172. Kim, C. J. et al.: Dendritic cells infected with poxviruses encoding: MART-1/Melan A sensitize T lymphocytes in vitro. J. Immunother., 20: 276-286 (1997).
173. Kim, J. J. et al.: Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes. Natl. Biotechnol., 15: 641-646 (1997).
174. Kim, J. J. et al.: Coadministration of IL-12 or IL-10 expression cassettes drives immune responses toward a Th1 phenotype. J. Interferon Cytokine Res., 18: 537-547 (1998).
175. Kirkin, A. F., K. Dzhandzhugazyan, and J. Zeuthen: The immunogenic properties of melanoma-associated antigens recognized by cytotoxic T lymphocytes. Exp. Clin Immunogenet., 15: 19-32 (1998).
176. Kittlesen, D. J. et al.: Human melanoma patients recognize an HLA-A1-restricted CTL epitope from tyrosinase containing two cysteine residues: implications for tumor vaccine development. J. Immunol., 160: 2099-2106 (1998).
177. Komata, T. et al.: B7-1(CD80)-transfected human glioma cells and interleukin-12 direCTLy stimulate allogeneic CD8(+) T cells. J. Immunother., 20: 256-264 (1997)
178. Korkolopoulou, P. et al.: Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. Br. J. Cancer, 73: 148-153 (1996).
179. Kowalczyk, D. et al.: Activated gamma/delta T lymphocytes infiltrating renal cell carcinoma. Immunol. Lett., 53: 15-18 (1996).
180. + cells are essential for allorejection. J. Exp. Med., 184: 2013-2018 (1996).
181. Kruit, W. H. J. et al.: Dose efficacy study of two schedules of high-dose bolus administration of interleukin-2 and interferon alpha in metastatic melanoma. Br. J. Cancer, 74: 951-955 (1996).
182. + cytotoxic T lymphocytes from tumor-infiltrating lymphocytes. Jpn. J. Cancer Res., 86: 135-139 (1995).
183. Kunihiro, M. et al.: Combined expression of HLA-DR antigen and proliferating cell nuclear antigen correlate with colorectal cancer prognosis. Oncology (Basel), 55: 326-333 (1998).
184. Lalvani, A. et al.: Optimization of a peptide-based protocol employing IL-7 for in vitro restimulation of human cytotoxic T-lymphocyte precursors. J. Immunol. Methods, 210: 65-77 (1997).
185. Leach, D. R. and G. N. Callahan: Fibrosarcoma cells expressing allogeneic MHC class II antigens induce protective antitumor immunity. J. Immunol., 154: 738-743 (1995).
186. Leach, D. R., M. F. Krummel, and J. P. Allison: Enhancement of antitumor immunity by CTLA-4 blockade. Science, 271: 1734-1736 (1996).
187. Lebelbinay, S. et al.: Experimental gene therapy of cancer using tumor cells engineered to secrete interleukin-13. Eur. J. Immunol., 25: 2340-2348 (1995).
188. Lee, D. S. et al.: Patterns of relapse and response to retreatment in patients with metastatic melanoma or renal cell carcinoma who responded to interleukin-2-based immunotherapy. Cancer J. Sci. Am., 4: 86-93 (1998).
189. Lee, J. et al.: Interleukin-2 expression by tumor cells alters both the immune response and the tumor microenvironment. Cancer Res., 58: 1478-1485 (1998).
190. Lefor, A. T. and D. F. Fabian: Enhanced cytolytic activity of tumor infiltrating lymphocytes (TILs) derived from an ICAM-1 transfected tumor in a murine model. J. Surg. Res., 75: 49-53 (1998).
191. Leimig, T. et al.: High-efficiency transduction of freshly isolated human tumor cells using adenoviral interleukin-2 vectors. Hum. Gene Ther., 7: 1233-1239 (1996).
192. + T lymphocytes by B7, a natural ligand for CD28, can be used to treat established mouse melanoma. J. Immunol., 153: 421-428 (1994).
193. Li, Y. W. et al.: Costimulation by CD48 and B7-1 induces immunity against poorly immunogenic tumors. J. Exp. Med., 183: 639-644 (1996).
194. Lin, K. Y. et al.: Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res., 56: 21-26 (1996).
195. Lin, W. C., S. Yasumura, and T. L. Whiteside: Transfer of interleukin-2 receptor genes into squamous cell carcinoma - modification of tumor cell growth. Arch. Otolaryngol. Head. Neck Surg., 119: 1229-1235 (1993).
196. Lin, W. C. et al.: Constitutive production of IL-2 by human carcinoma cells, expression of IL-2 receptor, and tumor cell growth. J. Immunol., 155: 4805-4816 (1995).
197. Lissoni, P. et al.: Clinical efficacy of cancer subcutaneous immunotherapy with interleukin-2 in relation to the pretreatment levels of tumor growth factor insulin-like growth factor-1. Tumori., 81: 261-264 (1995a).
198. Lissoni, P. et al.: Correlation between pretreatment serum levels of neopterin and response to interleukin-2 immunotherapy in cancer patients. J. Biol. Regulat. Homeost. Agent, 9: 21-23 (1995b).
199. Lissoni, P. et al.: Biological significance of interleukin-6 secretion on cancer immunotherapy with interleukin-2. Int. J. Immunother., 12: 49-52 (1996).
200. Lollini, P. L. et al.: Inhibition of tumor growth and enhancement of metastasis after transfection of the gamma-interferon gene. Int. J. Cancer, 55: 320-329 (1993).
201. Lollini, P. L. et al.: Transduction of genes coding for a histocompatibility (MHC) antigen and for its physiological inducer interferon-gamma in the same cell: efficient MHC expression and inhibition of tumor and metastasis growth. Hum. Gene Ther., 6: 743-752 (1995).
202. Lopez, M. et al.: Sequential biochemotherapy for metastatic colorectal cancer using, fluorouracil, folinic acid, thymopentin, and interleukin-2: clinical and immunological effects. Ann. Oncol., 6: 1011-1017 (1995).
203. Lynch, D. H. et al.: Flt3 ligand induces tumor regression and antitumor immune responses in vivo. Nature Med., 3: 625-631 (1997).
204. Ma, X. C. et al.: Expression of HLA-class II antigen in gastric carcinomas - its relationship to histopathological grade, lymphocyte infiltration, and five-year survival rate. Acta Oncol., 33: 187-190 (1994).
205. Maass, G. et al.: Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin-2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination. Proc. Natl. Acad. Sci. U.S.A., 92: 5540-5544 (1995).
206. Mackensen, A. et al.: Induction of tumor-specific cytotoxic T lymphocytes by immunization with autologous tumor cells and interleukin-2 gene transfected fibroblasts. J. Mol. Med-Jmm., 75: 290-296 (1997).
207. Mandelboim, O. et al.: Expression of two H-2K genes, syngeneic and allogeneic, as a strategy for potentiating immune recognition of tumor cells. Gene Therapy, 2: 757-765 (1995).
208. Mannering, S. I. et al.: HLA-DR1-restricted bcr-abl (b3a2)-specific CD4(+) T lymphocytes respond to dendritic cells pulsed with b3a2 peptide and antigen-presenting cells exposed to b3a2 containing cell lysates. Blood, 90: 290-297 (1997).
209. Marincola, F. M. et al.: HLA association with response and toxicity in melanoma patients treated with interleukin-2-based immunotherapy. Cancer Res., 52: 6561-6566 (1992)
210. Marincola, F. M. et al.: HLA associations in the antitumor response against malignant melanoma. J. Immunother., 18: 242-252 (1995).
211. Martin-Fontecha, A. et al.: Heterogeneous of B7-1 and B7-2 in the induction of both protective and therapeutic antitumor immunity against different mouse tumors. Eur. J. Immunol., 26: 1851-1859 (1996).
212. Martinotti, A. et al.: CD4 T cells inhibit in vivo the CD8-mediated immune response against murine colon carcinoma cells transduced with interleukin-12 genes. Eur. J. Immunol., 25: 137-146 (1995).
213. + lymphocytes for adoptive immunotherapy by selective leukapheresis (lymphocytapheresis). J. Hematother., 6: 253-260 (1997).
214. Masuda, Y. et al.: Suppression of in vivo tumor growth by the transfection of the interleukin-5 gene into colon tumor cells. Cancer Immunol. Immunother., 41: 325-330 (1995).
215. Matulonis, U. A. et al.: Role of B7-1 in mediating an immune response to myeloid leukemia cells. Blood, 85: 2507-2515 (1995).
216. Mayordomo, J. I. et al.: Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nature Med., 1: 1297-1302 (1995).
217. Mayordomo, J. I. et al.: Therapy of murine tumors with p53 wild-type and mutant sequence peptide-based vaccines. J. Exp. Med., 183: 1357-1365 (1996).
218. McAdam, A. J. et al.: Synergistic effects of coexpression of the Th1 cytokines IL-2 and IFN-gamma on generation of murine tumor-reactive cytotoxic cells. Int. J. Cancer, 61: 628-634 (1995).
219. McCarty, T. M. et al.: Targeting p53 for adoptive T-cell immunotherapy. Cancer Res., 58: 2601-2605 (1998).
220. McCune, C. S. et al.: Renal cell carcinoma treated by vaccines for active specific immunotherapy: correlation of survival with skin testing by autologous tumor cells. Cancer Immunol. Immunother., 32: 62-66 (1990).
221. McLaughlin, J. P. et al.: Improved immunotherapy of a recombinant carcinoembryonic antigen vaccinia vaccine when given in combination with interleukin-2. Cancer Res., 56: 2361-2367 (1996).
222. Melcher, A. et al.: Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nature Med., 4: 581-587 (1998).
223. Melero, I. et al.: AMPlification of tumor immunity by gene transfer of the costimulatory 4-1BB ligand: synergy with the CD28 costimulatory pathway. Eur. J. Immunol., 28: 1116-1121 (1998).
224. Melief, C. J. M. and W. M. Kast: T-cell immunotherapy of tumors by adoptive transfer of cytotoxic T lymphocytes and by vaccination with minimal essential epitopes. Immunol. Rev., 145: 167-177 (1995).
225. Melioli, G. et al.: Treatment of stage IIIB nonsmall-cell lung cancer with surgery followed by infusion of tumor infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J. Immunother., 19: 224-230 (1996).
226. Micallef, M. J. et al.: In vivo antitumor effects of murine interferon-gamma-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites. Cancer Immunol. Immunother., 43: 361-367 (1997).
227. Mihm, M. C., C. G. Clemente, and N. Cascinelli: Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response. Lab. Invest., 74: 43-47 (1996).
228. Miller, K. et al.: Improved survival of patients with melanoma with an antibody response to immunization to a polyvalent melanoma vaccine. Cancer, 75: 495-502 (1995).
229. Miyatake, S. et al.: Efficient tumor suppression by glioma-specific murine cytotoxic T lymphocytes transfected with interferon-gamma gene. JNCI, 82: 217-220 (1990).
230. + progenitors and from monocytes are not functionally equivalent antigen-presenting cells in the induction of Melan-A/Mart-1(27-35)-specific CTLs from peripheral blood lymphocytes of melanoma patients with low-frequency of CTL precursors. Cancer Res., 57: 5534-5541 (1997).
231. Mukherji, B. et al.: Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc. Natl. Acad. Sci. U.S.A., 92: 8078-8082 (1995).
232. Mulé, J. J. et al.: Disseminated human malignant melanoma in congenitally immune deficient (bg/nu/xid) mice. JNCI, 83: 350-356 (1991).
233. Mullen, C. A. et al.: Fibrosarcoma cells transduced with the IL-6 gene exhibit reduced tumorigenicity, increased immunogenicity, and decreased metastatic potential. Cancer Res., 52: 6020-6024 (1992).
234. Mullen, C. A. et al.: Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild-type tumor. Cancer Res., 54: 1503-1506 (1994).
235. Murphy, G. et al.: Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate, 29: 371-380 (1996).
236. Nabel, G. J. et al.: Direct gene transfer with DNA-liposome complexes in melanoma - expression, biologic activity, and lack of toxicity in humans. Proc. Natl. Acad. Sci. U.S.A., 90:11307-11311 (1993).
237. Nabel, G. J. et al.: Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA-liposome complexes Proc. Natl. Acad. Sci. U.S.A., 93: 15388-15393 (1996).
238. Naftzger, C. et al.: Immune response to a differentiation antigen induced by altered antigen: a study of tumor rejection and autoimmunity. Proc. Natl. Acad. Sci. U.S.A., 93: 14809-14814 (1996).
239. Nain, J. K. et al.: Antigen-presenting cells pulsed with unfractionated tumor-derived peptides are potent tumor vaccines. Eur. J. Immunol., 27: 589-597 (1997).
240. Naito, Y. et al.: CD8(+) T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res., 58: 3491-3494 (1998).
241. Nakamura, Y. et al.: Adoptive immunotherapy with murine tumor-specific T lymphocytes engineered to secrete interleukin-2. Cancer Res., 54: 5757-5760 (1994).
242. Negrier, S. et al.: Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N. Engl. J. Med., 338: 1272-1278 (1998).
243. Nelson, E. L. et al.: Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin's lymphoma. Blood, 88: 580-589 (1996).
244. Nestle, F. O. et al.: Vaccination of melanoma patients with peptide-or tumor lysate-pulsed dendritic cells. Nature Med., 4: 328-332 (1998).
245. Ogasawara, M. and S. A. Rosenberg: Enhanced expression of HLA molecules and stimulation of autologous human tumor infiltrating lymphocytes following transduction of melanoma cells with gamma-interferon genes. Cancer Res., 53: 3561-3568 (1993).
246. Olencki, T. et al.: Immunomodulatory effects of interleukin-2 and interleukin-4 in patients with malignancy. J. Immunother., 19: 69-80 (1996).
247. Onishi, T. et al.: Assessment of biological characteristics in renal cell carcinoma through patterns of tumour-infiltrating lymphocytes. Cancer J., 6: 123-129 (1993).
248. Ossendorp, F. et al.: Specific T helper cell requirements for optimal induction of cytotoxic T lymphocytes against major histocompatibility complex class II negative tumors. J. Exp. Med., 187: 693-702 (1998).
249. Ostrand-Rosenberg, S., A. Thakur, and V. Clements: Rejection of mouse sarcoma cells after transfection of MHC class II genes. J. Immunol., 144: 4068-4071 (1990).
250. Ostrand-Rosenberg, S. et al.: Expression of MHC class II and B7-1 and B7-2 costimulatory molecules accompanies tumor rejection and reduces the metastatic potential of tumor cells. Tissue Antigens, 47: 414-421 (1996).
251. Paglia, P. et al.: Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo. J. Exp. Med., 183: 317-322 (1996).
252. Palomares, T. et al.: The addition of interleukin-2 to cyclophosphamide therapy can facilitate tumor growth of B16 melanoma. Cancer Immunol. Immunother., 40: 292-298 (1995).
253. Patel, P. M. et al.: Cytokine gene transfer as a therapeutic strategy. J. Immunother, 14: 310-313 (1993).
254. Pawelec, G. et al.: Dissection of suppressor cell generation in vitro. Hum. Immunol , 17: 343-354 (1986).
255. Pawelec, G. et al.: Interleukin-10 protects activated human T lymphocytes against growth factor withdrawal-induced cell death but only anti-fas antibody can prevent activation-induced cell death. Cytokine, 8: 877-881 (1996).
256. Pawelec, G., J. Zeuthen, and R. Kiessling: Escape from host-antitumor immunity. Crit. Rev. Oncogenesis, 8: 111-145 (1997).
257. Pecher, G. and O. J. Finn: Induction of cellular immunity in chimpanzees to human tumor-associated antigen mucin by vaccination with MUC-1 cDNA-transfected Epstein-Barr virus immortalized autologous B cells. Proc. Natl. Acad. Sci. U.S.A., 93: 1699-1704 (1996).
258. Plaksin, D. et al.: Effective antimetastatic melanoma vaccination with tumor cells transfected with MHC genes and/or infected with Newcastle disease virus (NDV). Int. J. Cancer, 59: 796-801 (1994).
259. Plautz, G. E. et al.: Systemic T-cell adoptive immunotherapy of malignant gliomas. J. Neurosurg., 89: 42-51 (1998).
260. Plebanski, M. et al.: Induction of peptide-specific primary cytotoxic T lymphocyte responses from human peripheral blood. Eur. J. Immunol., 25: 1783-1787 (1995).
261. Porgador, A. et al.: Combined vaccination with major histocompatibility Class I and interleukin-2 gene-transduced melanoma cells synergizes the cure of postsurgical established lung metastases. Cancer Res., 55: 4941-4949 (1995).
262. Porgador, A., D. Snyder, and E. Gilboa: Induction of antitumor immunity using bone marrow-generated dendritic cells. J. Immunol., 156: 2918-2926 (1996).
263. Prehn, R. T. and L. M. Prehn: The flip side of tumor immunity. Arch. Surg., 124: 102-106 (1989).
264. Protti, M. P. et al.: Particulate naturally processed peptides prime a cytotoxic response against human melanoma in vitro. Cancer Res., 56: 1210-1213 (1996).
265. Pulaski, B. A. and S. Ostrand-Rosenberg: Reduction of established spontaneous mammary carcinoma metastases following immunotherapy with major histocompatibility complex class II and B7.1 cell-based tumor vaccines. Cancer Res., 58: 1486-1493 (1998).
266. Pulaski, B. A. et al.: Interleukin-3 enhances development of tumor-reactive cytotoxic cells by a CD4-depend nt mechanism. Cancer Res., 53: 2112-2117 (1993).
267. Pulaski, B. A. et al.: Interleukin-3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "representation" of exogenous antigen by tumor-infiltrating antigen-presenting cells. Proc. Natl. Acad. Sci. U.S.A., 93: 3669-3674 (1996).
268. Puolakkainen, P. et al.: Increase of plasma transforming growth factor beta (TGF beta) during immunotherapy with IL-2. Cancer Invest., 13: 583-589 (1995).
269. Putzer, B. M. et al.: Interleukin-12 and B7-1 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression. Proc. Natl. Acad. Sci. U.S.A., 94: 10889-10894 (1997).
270. Ravaud, A. et al.: Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastic renal cell carcinoma: a multicenter phase II trial. J. Clin. Oncol., 16: 2728-2732 (1998).
271. Reddish, M. A. et al.: Anti-MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide. Int. J. Cancer, 76: 817-823 (1998).
272. Reeves, M. E. et al.: Retroviral transduction of human dendritic cells with a tumor-associated antigen gene. Cancer Res., 56: 5672-5677 (1996).
273. + T-cell responses to MAGE-3 and Melan A MART-1 by immunization to a polyvalent melanoma vaccine. Int. J. Cancer, 72: 972-976 (1997).
274. Ribas, A. et al.: Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant adenovirus-transduced murine dendritic cells. Cancer Res., 57: 2865-2869 (1997).
275. Ridolfi, R. et al.: Adjuvant adaptive immunotherapy with tumor-infiltrating lymphocytes and modulated doses of interleukin-2 in 22 patients with melanoma, colorectal and renal cancer, after radical metastasectomy, and in 12 advanced patients. Cancer Immunol. Immunother., 46: 185-193 (1998).
276. Rockett, J. C. et al.: Lymphocyte infiltration in oesophageal carcinoma: lack of correlation with MHC antigens, ICAM-1, and tumor stage and grade. J. Clin. Pathol., 49: 264-267 (1996).
277. Ropke, M. et al.: Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide. Proc. Natl. Acad. Sci. U.S.A., 93: 14704-14707 (1996).
278. Roselli, M. et al.: Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen. J. Clin. Oncol., 14: 2031-2042 (1996).
279. Rosenberg, S. A. et al.: Gene transfer into humans - immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N. Engl. J. Med., 323: 570-578 (1990).
280. Rosenberg, S. A. et al.: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose Bolus interleukin-2. JAMA, 271: 907-913 (1994a).
281. Rosenberg, S. A. et al.: Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin-2. J. Nat. Cancer Inst., 86: 1159-1166 (1994b).
282. Rosenberg, S. A. et al.: Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nature Med., 4: 321-327 (1998).
283. Rosenthal, F. M. et al.: Augmentation of antitumor immunity by tumor cells transduced with a retroviral vector carrying the interleukin-2 and interferon-gamma cDNAs. Blood, 83: 1289-1298 (1994).
284. Rotzschke, O., K. Falk, and J. L. Strominger: Superactivation of an immune response triggered by oligomerized T-cell epitopes. Proc. Natl. Acad. Sci. U.S.A., 94: 14642-14647 (1997).
285. Rubin, J. et al.: Phase I study of immunotherapy of hepatic metastases of colorectal carcinoma by direct gene transfer. Hun . Gene Ther., 5: 1385-1399 (1994).
286. Rubin, J. et al.: Phase I study of immunotherapy of hepatic metasta es of colorectal carcinoma by direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7. Gene Therapy, 4: 419-25 (1997).
287. Ruzek, M. C. and A. Mathur: In vitro and in vivo recovery of IFN-gamma, but not IL-2, production by IL-12 in mice with plasma cell tumors. Int. Immunol., 8: 413-422 (1996).
288. Sabzevari, H. and R. A. Reisfeld: Human cytotoxic T-cells suppress the growth of spontaneous melanoma metastases in SCID/hu mice. Cancer Res., 53: 4933-4937 (1993).
289. Sadanaga, N. et al.: Local immune response to tumor invasion in esophageal squamous cell carcinoma - the expression of human leukocyte antigen-DR and lymphocyte infiltration. Cancer, 74: 586-591 (1994).
290. Salgaller, M. L. et al.: Immunization against epitopes in the human melanoma antigen gplOO following patient immunization with synthetic peptides. Cancer Res., 56: 4749-4757 (1996).
291. Salgaller, M. L. et al.: Report of immune monitoring of prostate cancer patients undergoing T-cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen (PSMA). Prostate, 35: 144-151 (1998).
292. Sato, J. et al.: Enhancement of antitumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2. Biotherapy, 6: 225-231 (1993).
293. Schachter, J. et al.: A sequential four-drug chemotherapy and biotherapy with interferon alpha and GM-CSF - an innovative protocol for the treatment of metastatic melanoma. Cancer Biother. Radiopharm., 13: 155-164 (1998).
294. Scheibenbogen, C. et al.: Expression of gp100 in melanoma metastases resected before or after treatment with IFN alpha and IL-2. J. Immunother., 19: 375-380 (1996).
295. Schendel, D. J. and B. Gansbacher: Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes - modulation of recognition through retroviral transduction of tumor cells with interleukin-2 complementary DNA and exogenous alpha-interferon treatment. Cancer Res., 53: 4020-4025 (1993).
296. Schlom, J. et al.: Strategies for the development of recombinant vaccines for the immunotherapy of breast cancer. Breast Cancer Res. Treat., 38: 27-39 (1996).
297. Schmidt, W. et al.: Cell-free tumor antigen peptide-based cancer vaccines. Proc. Natl. Acad. Sci. U.S.A., 94: 3262-3267 (1997).
298. Schoenberg, S. P. et al.: T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature, 393: 480-483 (1998).
299. Schuler, M. et al.: Lack of efficacy of recombinant human interleukin-6 in patients with advanced renal cell cancer: results of a phase II study. Eur. J. Cancer, 34: 754-756 (1998).
300. Schwartzentruber, D. J. et al.: In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2. J. Clin. Oncol., 12: 1475-1483 (1994).
301. Selvaggi, T. A., R. E. Walker, and T. A. Fleisher: Development of antibodies to fetal calf serum with arthus-like reactions in human immunodeficiency virus-infected patients given syngeneic lymphocyte infusions. Blood, 89: 776-779 (1997).
302. Sensi, M. et al.: Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a hapten-modified autologous tumor vaccine. J. Clin. Invest., 99: 710-717 (1997).
303. Sensi, M. et al.: Intralesional selection of T-cell clonotypes in the immune response to melanoma antigens occurring during vaccination. J. Immunother., 21: 198-204 (1998)
304. Simons, J. W. et al.: Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer. Cancer Res., 57: 1537-1546 (1997).
305. Simpson, W. G. et al.: Acute phase proteins and recombinant IL-2 therapy: prediction of response and survival in patients with colorectal cancer. Clin. Exp. Immunol., 99: 143-147 (1995).
306. Sparano, J. A. et al.: Randomized phase-III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. J. Clin. Oncol., 11: 1969-1977 (1993).
307. Sporn, J. R. et al.: Adoptive immunotherapy with peripheral blood lymphocytes cocultured in vitro with autologous tumor cells and interleukin-2. Cancer Immunol. Immunother., 37: 175-180 (1993).
308. Stadler, W. M. et al.: Multicenter phase II trial of interleukin-2, interferon alpha and 13-cis-retinoic acid in patients with metatstatic renal cell carcinoma. J. Clin. Oncol., 16: 1820-1825 (1998).
309. + selected renal cell carcinoma tumor-infiltrating lymphocytes (TIL) - evidence for enhanced specific killing of tumor necrosis factor-secreting IL-6 nonsecreting TIL in vitro and correlation with complete response in vivo. Clin. Immunol. Immunopathol., 72: 237-247 (1994).
310. Stenholm, A. C. O., A. F. Kirkin, and J. Zeuthen: In vivo eradication of an established human melanoma by an in vitro generated autologous cytotoxic T-cell clone: a seid mouse model. Int. J. Cancer, 77: 476-480 (1998).
311. Steptoe, R. J. et al.: Augmentation of dendritic cells in murine organ donors by Flt3 ligand alters the balance between transplant tolerance and immunity. J. Immunol., 159: 5483-5491 (1997).
312. Stoppacciaro, A. et al.: Regression of an established tumor genetically modified to release granulocyte colony-stimulating factor requires granulocyte T-Cell cooperation and T-cell produced interferon-gamma. J. Exp Med., 178: 151-161 (1993).
313. Stoppacciaro, A. et al.: Genetic modification of a carcinoma with the IL-4 gene increases the influx of dendritic cells relative to other cytokines. Eur. J. Immunol., 27: 2375-2382 (1997).
314. Straten, P. T. et al.: Activation of preexisting T-cell clones by targeted interleukin-2 therapy. Proc. Natl. Acad. Sci. U.S.A., 95: 8785-8790 (1998).
315. Strome, S. E. et al.: Secretion of both IL-2 and IL-4 by tumor cells results in rejection and immunity. J. Immunother., 19: 21-32 (1996).
316. Suminami, Y. et al.: In situ interleukin-4 gene expression in cancer patients treated with genetically modified tumor vaccine. J. Immunother., 17: 238-248 (1995).
317. Sun, W. H. et al.: In vivo and in vitro characteristics of interleukin-6-transfected B16 melanoma cells. Cancer Res., 52: 5412-5415 (1992).
318. Sun, Y. et al.: Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Therapy, 5: 481-490 (1998).
319. Suto, R. and P. K. Srivastava: A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science, 269: 1585-1588 (1995).
320. Suzuki, T. et al.: Viral interleukin-10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors. J. Exp. Med., 182: 477-486 (1995).
321. Taga, K., B. Cherney, and G. Tosato: IL-10 inhibits apoptotic cell death in human T-cells starved of IL-2. Int. Immunol., 5: 1599-1608 (1993).
322. Tamura, Y. et al.: Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science, 278: 117-120 (1997).
323. Tan, M. C. A. A. et al.: Mannose receptor-mediated uptake of antigens strongly enhances HLA class II-restricted antigen presentation by cultured dendritic cells. Eur. J. Immunol., 27: 2426-2435 (1997).
324. Tanaka, F. et al.: Efficient induction of antitumor cytoxic T lymphocytes from a healthy donor using HLA-A2-restricted MAGE-3 peptide in vitro. Cancer Immunol. Immunother., 44: 21-26 (1997).
325. Tartour, E. et al.: Predictors of clinical response to interleukin-2 based immunotherapy in melanoma patients: a french multiInstitutional study. J. Clin. Oncol., 14: 1697-1703 (1996).
326. Tasaki, K. et al.: Induction of T-cell dependent acquired immunity in syngeneic mice by the combined expression of interleukin-4 and granulocyte macrophage-colony stimulating factor gene in murine colon carcinoma cells. Anticanc er Res., 18: 1453-1456 (1998).
327. Tatsumi, T. et al.: Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma. Hepatology, 25: 1108-1114 (1997).
328. Tepper, R. I., P. K. Pattengale, and P. Leder: Murine interleukin-4 displays potent antitumor activity in vivo. Cell, 57: 503-512 (1989).
329. Theobald, M. et al.: Targeting p53 as a general tumor antigen. Proc. Natl. Acad. Sci. U.S.A., 92: 11993-11997 (1995).
330. Tjoa, B. A. et al.: Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides. Prostate, 36: 39-44 (1998).
331. Toes, R. E. M. et al.: Protective anti-tumor immunity induced by vaccination with recombinant adenoviruses encoding multiple tumor-associated cytotoxic T lymphocyte epitopes in a string-of-beads fashion. Proc. Natl. Acad. Sci. U.S.A., 94: 14660-14665 (1997).
332. + T cells in cancer immunotherapy. Curr. Opin. Immunol., 6: 741-745 (1994).
333. + T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes. J. Exp. Med., 183: 1965-1971 (1996).
334. Townsend, S. E. et al.: Specificity and longevity of antitumor immune responses induced by B7-transfected tumors. Cancer Res., 54: 6477-6483 (1996).
335. Triozzi, P. L. and W. Aldrich: Phenotypic and functional differences between human dendritic cells derived in vitro from hematopoietic progenitors and from monocytes macrophages. J. Leukocyte Biol., 61: 600-608 (1997).
336. Tsavaris, N. et al.: The prognostic significance of immune changes in patients with renal cancer, melanoma, and colorectal cancer, treated with interferon-alpha 2b. Cancer Immunol. Immunother., 43: 94-102 (1996).
337. Tulp, A. et al.: Isolation and characterization of the intracellular MHC class II compartment. Nature, 369: 120-126 (1994).
338. Vagliani, M. et al.: Interleukin-12 potentiates the curative effect of a vaccine based on interleukin-2-transduced tumor cells. Cancer Res., 56: 467-470 (1996).
339. Van Elsas, A. et al.: Peptide-pulsed dendritic cells induce tumoricidal cytotoxic T lymphocytes from healthy donors against stably HLA-A *0201-binding peptides from the Melan-A/MART-1 self antigen. Eur. J. Immunol., 26: 1683-1689 (1996).
340. Van Elsas, A. et al.: UV-induced N-ras mutations are T-cell targets in human melanoma. Melanoma Res., 7: S107-S113 (1997).
341. Van Haesebroeck, B. et al.: Expression of the tumor necrosis factor gene in tumor cells correlates with reduced tumorigenicity and reduced invasiveness in vivo. Cancer Res., 51: 2229-2238 (1991).
342. van Hall, T. et al.: Cryptic open reading frames in plasmid vector backbone sequences can provide highly immunogenic cytotoxic T-lymphocyte epitopes. Cancer Res., 58: 3087-3093 (1998).
343. Veelken, H. et al.: A phase-I clinical study of autologous tumor cells plus interleukin-2 gene transfected allogeneic fibroblasts as a vaccine in patients with cancer. Int. J. Cancer, 70: 269-277 (1997).
344. Vierboom, M. P. M. et al.: Tumor eradication by wild-type p53-specific cytotoxic T lymphocytes. J. Exp. Med., 186: 695-704 (1997).
345. Vile, R. G. et al.: Systemic gene therapy of murine melanoma using tissue specific expression of the HSVtk gene involves an immune component. Cancer Res., 54: 6228-6234 (1994).
346. Visseren, M. J. W. et al.: Production of interleukin-2 by E14 tumor cells induces natural killer cell and T-cell mediated immunity. J. Immunother., 15: 119-128 (1994).
347. Vlock, D. R. et al.: Phase II trial of interferon-alpha in locally recurrent or metastatic squamous cell carcinoma of the head and neck: immunological and clinical correlates. J. Immunother., 19: 433-442 (1996).
348. Vogelzang, N. J., T. M. Lestingi, and G. Sudakoff: Phase I study of immunotherapy of metastatic renal cell carcinoma by direct gene transfer into metastatic lesions. Hum. Gene Ther., 5: 1357-1370 (1994).
349. Vora, A. R. et al.: An immunohistochemical study of altered immunomodulatory molecule expression in head and neck squamous cell carcinoma. Br. J. Cancer, 76: 836-844 (1997).
350. Wahl, W. L. et al.: Generation of therapeutic T-lymphocytes after in vivo tumor transfection with an allogeneic class I major histocompatibility complex gene. J. Immunother., 17: 1-11 (1995).
351. Wakimoto, H. et al.: Intensified antitumor immunity by a cancer vaccine that produces granulocyte-macrophage colony-stimulating factor plus interleukin-4. Cancer Res., 56: 1828-1833 (1996).
352. Waldmann, T. A.: The IL-2/IL-2 receptor system - a target for rational immune intervention. Immunol. Today, 14: 264-270 (1993).
353. Wallack, M. K. et al.: A phase III randomized, double-blind, multiInstitutional trial of vaccinia melanoma oncolysate-active specific immunotherapy for patients with stage II melanoma. Cancer, 75: 34-42 (1995).
354. Wallack, M. K. et al.: Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial. J. Am. Coll. Surgeons, 187: 69-77 (1998).
355. Walsh, C. M. et al.: Cell-mediated cytotoxicity results from, but may not be cntical for, primary allograft rejection. J. Immunol., 156: 1436-1441 (1996).
356. Walter, E. A. et al.: Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N. Engl. J. Med., 333: 1038-1044 (1995).
357. Wang, B. et al.: Immunization by direct DNA inoculation induces rejection of tumor cell challenge. Hum. Gene Ther., 6: 407-418 (1995).
358. Wang, Y. C. et al.: Induction of autologous tumor-specific cytotoxic T-lymphocyte activity against a human renal carcinoma cell line by B7-1 (CD80) costimulation. J. Immunother., 19: 1-8 (1996).
359. Watanabe, Y. et al.: Exogenous expression of mouse interferon gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigemcity by augmented antitumor immunity. Proc. Natl. Acad. Sci. U.S.A., 86: 9456-9460 (1989).
360. Weidmann, E. et al.: Evidence for oligoclonal T-cell response in a metastasis of renal cell carcinoma responding to vaccination with autologous tumor cells and transfer of in vitro sensitized vaccine-draining lymph node lymphocytes. Cancer Res., 53: 4745-4749 (1993).
361. Wendtner, C. M. et al.: Gene transfer of costimulatory molecules B7-1 and B7-2 into human multiple myeloma cells by recombinant adeno-associated virus enhances the cytolytic T-cell response. Gene Therapy, 4: 726-735 (1997).
362. Wentworth, P. A. et al.: In vitro induction of primary, antigen-specific CTL from human peripheral blood mononuclear cells stimulated with synthetic peptides. Mol. Immunol., 32: 603-612 (1995).
363. White, C. A. et al.: Constitutive transduction of peptide transporter and HLA genes restores antigen processing function and cytotoxic T-cell-mediated immune recognition of human melanoma cells. Int. J. Cancer, 75: 590-595 (1998).
364. Whitehead, R. P. et al.: A phase II trial of continuous-infusion recombinant interleukin-2 in patients with advanced renal cell carcinoma: a Southwest Oncology Group Study. J. Immunother., 18: 104-114 (1995).
365. Xu, X. L. et al.: IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for upregulation of Fas and FasL expression. Cancer Res., 58: 2832-2837 (1998).
366. + activation antigens on peripheral blood lymphocyte populations in metastatic breast and ovarian cancer patients: correlations with survival following active specific immunotherapy. Int. J. Cancer, 61: 470-474 (1995).
367. Yahata, T. et al.: Accumulation of IL-12 activated antitumor effector cells into lymph nodes of tumor bearing mice. Immunol. Lett., 61: 127-133 (1998).
368. Yamaue, H. et al.: Enhanced interleukin-2 production in human tumor-infiltrating lymphocytes engineered by 3′-truncated interleukin-2 gene. J. Immunother., 16: 262-274 (1994).
369. Yang, G. C. et al.: Antitumor immunity elicited by tumor cells transfected with B7-2, a second ligand for CD28/ CTLA-4 costimulatory molecules. J. Immunol., 154: 2794-2800 (1995a).
370. Yang, G. C. et al.: In vitro priming of tumor-reactive cytolytic T lymphocytes by combining IL-10 with B7-CD28 costimulation. J. Immunol., 155: 3897-3903 (1995b).
371. Yang, S. X., T. L. Darrow, and H. F. Seigler: Generation of primary tumor-specific cytotoxic T lymphocytes from autologous and human lymphocyte antigen class I-matched allogeneic peripheral blood lymphocytes by B7 gene-modified melanoma cells. Cancer Res., 57: 1561-1568 (1997).
372. Yannelli, J. R. et al.: Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience. Int. J. Cancer, 65: 413-421 (1996).
373. Yasumura, S. et al.: Expression of interleukin-2 receptors on human carcinoma cell lines and tumor growth inhibition by interleukin-2. Int. J. Cancer, 59: 225-234 (1994)
374. + T-cell clones from the peripheral blood of melanoma patients following in vitro stimulation with recombinant vaccinia virus. J. Immunol., 157: 4079-4086 (1996).
375. Zajac, P. et al.: Generation of tumoricidal cytotoxic T lymphocytes from healthy donors after in vitro stimulation with a replication-incompetent vaccinia virus encoding MART-1/ Melan-A 27-35 epitope. Int. J. Cancer, 71: 491-496 (1997).
376. Zarour, H. et al.: The majority of autologous cytolytic T-lymphocyte clones derived from peripheral blood lymphocytes of a melanoma patient recognize an antigenic peptide derived from gene Pme117/gp100. J. Invest. Dermatol., 107: 63-67 (1996).
377. Zatloukal, K. et al.: Elicitation of a systemic and protective antimelanoma immune response by an IL-2 based vaccine - assessment of critical cellular and molecular parameters. J. Immunol., 154: 3406-3419 (1995).
378. Zier, K. S. and B. Gansbacher: Tumour cell vaccines that secrete interleukin-2 (IL-2) and interferon gamma (IFN gamma) are recognised by T cells while resisting destruction by natural killer (NK) cells. Eur. J. Cancer, 32A: 1408-1412 (1996)
379. Zitvogel, L. et al.: Interleukin-12 and B7.1 costimulation cooperate in the induction of effective antitumor immunity and therapy of established tumors. Eur. J. Immunol., 26: 1335-1341 (1996a).
380. Zitvogel, L. et al.: Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines. J. Exp. Med., 183: 87-97 (1996b).
381. Zitvogel, L. et al.: Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nature Med., 4: 594-600 (1998).
382. Zou, J. P. et al.: Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-gamma production by antitumor T cells. Int. Immunol., 7: 1135-1145 (1995).