Update on cancer vaccines

Current Opinion in Gastroenterology

Volumn 18, Issue 6, 2002, Pages 723-731

  Borges, Virginia F ^a   Kufe, Donald ^a   Avigan, David E ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALUMINUM POTASSIUM SULFATE; CANCER VACCINE; CARCINOEMBRYONIC ANTIGEN; CD40 LIGAND; DNA VACCINE; FREUND ADJUVANT; INTERLEUKIN 12; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MUCIN 1; PEPTIDE; PHOSPHORYL LIPID A; TUMOR ANTIGEN;

ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; CANCER IMMUNOTHERAPY; CYTOTOXIC T LYMPHOCYTE; DENDRITIC CELL; HUMAN; IMMUNE RESPONSE; LYMPHOMA; MELANOMA; NONHUMAN; REVIEW; T LYMPHOCYTE ACTIVATION; TUMOR CELL; TUMOR IMMUNITY; VACCINATION; VIRAL GENE THERAPY;

EID: 0036827754     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001574-200211000-00015     Document Type: Review

References (106)

1. Boon T, van der Bruggen P: Human tumor antigens recognized by T lymphocytes. J Exp Med 1996, 183:725-729.
2. Renkvist N, Castelli C, Robbins PF, et al.: A listing of human tumor antigens recognized by T cells. Cancer Immunol Immunotherapy 2001, 50:3-15. Contains a comprehensive list of all tumor antigens and their major peptides recognized by T cells with explanation of the categorization of these antigens.
3. Rosenberg SA: The immunotherapy of solid cancer based on cloning the genes encoding tumor-rejection antigens. Annu Rev Med 1996, 47:481-491.
4. Harding FA, McArthur JG, Gross JA, et al.: CD28-mediated signaling costimulates murine T cells and prevents induction of anergy in T cell clones. Nature 1992, 356:607-609.
5. Caux C, Massacrier C, Vanbervliet B, et al.: Activation of human dendritic cells through CD40 cross-linking. J Exp Med 1994, 180:1263-1272.
6. McLellan AD, Sorg RV, Williams LA, et al.: Human dendritic cells activate T lymphocytes via a CD40: CD40-ligand dependent pathway. Eur J Immunol 1996, 26:1204-1210.
7. Macatonia SE, Hosken NA, Litton M, et al.: Dendritic cells produce IL-12 and direct the development of Th1 cells from naïve CD4+ T cells. J Immunol 1995, 154:5071-5079.
8. Carrel S, Johnson JP: Immunologic recognition of malignant melanoma by autologous T lymphocytes. Curr Opin Oncol 1993, 5:383-389.
9. Cox AL, Skipper J, Che Y, et al.: Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines, Science 1994, 264:716-719 1994.
10. Kawakami Y, Eliyahu S, Delgaro CH, et al.: Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci USA 1994, 91:6458-6462.
11. Speiser DE, Miranda R, Zakarian A, et al.: Self antigens expressed by solid tumors do not efficiently stimulate naïve or activated T cells: Implications for immunotherapy. J Exp Med 1997, 186:645-653.
12. Staveley-O'Carroll K, Sotomayer E, Montgomery J, et al.: Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. Proc Natl Acad Sci USA 1998, 95:1178-1183.
13. Bell D, Chomarat P, Broyels D, et al.: In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 1999, 190:1417-1426.
14. Salgaller ML, Marincola FM, Cormier JN, et al.: Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides. Cancer Res 1996, 56:4749-4757.
15. Marchand M, Weynants P, Rankin E, et al.: Tumor regression responses in melanoma patients treated with peptide encoded by gene Mage-3 [letter]. Int J Cancer 1995, 63:883.
16. Rosenberg SA, Yang JC, Schwartzentruber DJ, et al.: Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nature Med 1998, 8:321-327.
17. Jager E, Ringhoffer M, Dienes HP, et al.: Granulocyte-macrophage colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int J Cancer 1996, 67:54-62.
18. Chianese-Bullock KA, Slingluff CL.: Peptide vaccines for cancer. Principles and Practice of Biologic Therapy of Cancer 2002, 3(suppl 1):1-16.
19. Piechocki MP, Pilson SA, Wei WZ: Complementary antitumor immunity induced by plasmid DNA encoding secreted and cytoplasmic human ErbB-2. J Immunol 2001, 167:3367-3374.
20. Rice J, Elliot T, Buchan S: DNA fusion vaccine designed to induce cytotoxic T cell responses against defined peptide motifs: Implications for cancer vaccines. J Immunol 2001, 167:1558-1565.
21. Miconnet I, Coste I, Beermann F, et al.: Cancer vaccine design: A novel bacterial adjuvant for peptide-specific CTL induction. J Immunol 2001, 166:4612-4619.
22. Mattner F, Fleitmann JK, Lingnau K, et al.: Vaccination with poly-L-arginine as immunostimulatant for peptide vaccines: Induction of potent and long-lasting T cell responses against cancer antigens. Cancer Res 2002, 62:1477-1480.
23. Le Gal FA, Prevost-Blondel A, Lengagne R, et al.: Lipopeptide-based melanoma cancer vaccine induced a strong MART-27-35 cytotoxic T lymphocyte response in a preclinical study. Int J Cancer 2002, 98:221-227.
24. Ohnmacht GA, Wong E, Mocellin S, et al.: Short-term kinetics of tumor antigen expression in response to vaccination. J Immunol 2001, 167:1809-1820. Reports on serial assessment of identical metastatic lesions over time obtained during treatment of cancer vaccines. Immune selection is demonstrated to be heterogeneous and not linked to clinical outcome in the metastatic lesion. A significant change in gene expression patterns in responding versus nonresponding metastatic lesions is demonstrated.
25. Rosenberg SA: Progress in human tumor immunology and immunotherapy. Nature 2001, 411:380-384. Offers an overview of the rationale for immunotherapy of cancer and highlights the ongoing questions and issues in cancer vaccine development.
26. Xiang R, Silletti S, Lode HN, et al.: Protective immunity against human carcinoembryonic antigen (CEA) induced by an oral DNA vaccine in CEA-transgenic mice. Clin Cancer Res 2001, 3:856s.
27. Vollmer CM, Eilber FC, Butterfield LH, et al.: Alpha-fetoprotein-specific immunotherapy for hepatocellular carcinoma. Cancer Res 1999, 59:3064-3067.
28. Sun X, Hodge LM, Jones HP, et al.: Co-expression of granulocyte-macrophage colony-stimulating factor with antigen enhances humoral and tumor immunity after DNA vaccination. Vaccine 2002, 20:1466-1474.
29. Sedegah M, Weiss W, Sacci JB, et al.: Improving protective immunity induced by DNA-based immunization; priming with antigen and GM-CSF encoding plasmid DNA and boosting with recombinant antigen-expressing poxvirus. J Immunol 2000, 164:5905-5912.
30. Xiang R, Primus J Ruehlmann JM, et al.: A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice. J Immunol 2001, 167:4560-4565.
31. Nishitani MS, Sakai T, Ishii K, et al.: A convenient cancer vaccine therapy with in vivo transfer of interleukin 12 expression plasmid using gene gun technology after priming with irradiated carcinoma cells. Cancer Gene Ther 2002, 9:156-163.
32. Akagi J, Hodge JW, McLaughlin JP, et al.: Therapeutic antitumor response after immunization with an admixture of recombinant vaccinia viruses expressing modified MUC1 gene and the murine T-cell costimulatory molecule B7. J Immunother 1997, 20:38-47.
33. Liu DW, Tsao YP, Hsieh CH, et al.: Induction of CD8 T cells by vaccination with recombinant adenovirus expressing human papillomavirus type 16E5 gene reduces tumor growth. J Virol 2000, 74:9083-9089.
34. Hodge JW, McLaughlin JP, Abrams SI, et al.: Admixture of a recombinant vaccinia virus containing the gene for 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 1995,55:3598-3603.
35. Grosenbach DW, Barrientos JC, Schlom J, et al.: Synergy of vaccine strategies to amplify antigen-specific immune responses and antitumor effects. Cancer Res 2001, 61:4497-4505. The authors meticulously delineate a stepwise enhancement of CEA-specific T-cell responses for the CEA tumor antigen using a solitary co-stimulatory molecule adjuvant, followed by a triad of co-stimulatory molecules known as TRICOM, then adding GM-CSF to the triad, abd, lastly, by using different vectors for the prime versus boost vaccination in a CEA transgenic murine model.
36. Irvine KR, Chanberlain RS, Shulman EP, et al.: Enhancing efficacy of recombinant anticancer vaccines with prime/boost regimens that use two different vectors. J Natl Cancer Inst 1997, 89:1595-1601.
37. Meng WS, Butterfield LH, Ribas A, et al.: Alpha-fetoprotein-specific tumor immunity induced by plasmid prime-adenovirus boost genetic vaccination. Cancer Res 2001, 61:8782-8786. Focuses on a vaccine strategy targeting alpha-fetoprotein for hepatocellular carcinoma. Limited data have thus far been presented on immunotherapy for this cancer despite being a major cause of death worldwide. The authors outline a prime-boost strategy of naked DNA vaccine followed by boosting with an adenoviral vector, both specific for alpha-fetoprotein, which demonstrates enhanced tumor antigen-specific killing over DNA vaccination alone. This cell-free technique may be of particlular interest in a cancer that predominates in countries where the ability to generate cell-based vaccination is compromised by limited healthcare.
38. Baskar S, Ostrand-Rosenberg S, Nabavi N, et al.: Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated major histocompatability complex class II molecules. Proc Natl Acad Sci USA 1993, 90:5687-5690.
39. Townsend SE, Allison JP: Tumor rejection after direct costimulation of CD8+ T cell by B7 transfected melanoma cells. Science 1993, 259:368-370.
40. Ogasawara M, Rosenberg SA: Enhanced expression of HLA molecules and stimulation of autologous human tumor infiltrating lymphocytes following transduction of melanoma cells with gamma-interferon genes. Cancer Res 1993, 53:3561-3568.
41. Uchiyama A, Hoon DS, Morisaki T, et al: Transfection of interleukin-2 gene into human melanoma cells augments cellular immune response. Cancer Res 1993, 53:949-952.
42. Simons JW, Mikhak B, Chang JF, et al.: Induction of immunity to prostate cancer antigens, results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res 1999, 59:5160-5168.
43. Soiffer R, Lynch T, Mihm M, et al.: Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci USA 1998, 95:13141-13146.
44. Jaffe EM, Abrahms R, Cameron J, et al.: A phase I clinical trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene for the treatment of pancreatic adenocarcinoma. Hum Gene Ther 1998, 9:1951-1971.
45. Roth J, Molldrem J, Smythe WR: The current status of cancer gene therapy trials. In: Rosenberg SA, ed. Cancer, Principles and Practice of Oncology, 5th Ed. Cedar Knolls, NJ: Lippincott Williams & Wilkins Healthcare; 1999:13(11).
46. Hock H, Dorsch M, Kunzendorf U, et al.: Vaccinations with tumor cells genetically engineered to produce different cytokines: Effectivity not superior to a classical adjuvant. Cancer Res 1993, 53:714-716.
47. Mitchell MS: Perspective on allogeneic melanoma lysates in active specific immunotherapy, Semin Oncology 1998, 25:623-635.
48. Bystryn JC: Clinical activity of a polyvalent melanoma antigen vaccine. Recent Results Cancer Res 1995, 139:337-348.
49. Morton DL, Hoon DS, Nizze JA, et al.: Polyvalent melanoma vaccine improves survival of patients with metastatic melanoma, Ann NY Acad Sci 1993, 690:120-134.
50. Nanni P, Nicoletti G, De Giovanni C: Combined allogeneic tumor cell vaccination and systemic interleukin-12 prevents mammary carcinogenesis in Her 2/neu transgenic mice. J Exp Med 2001, 194:1195-1205.
51. Machiels JP, Reilly RT, Emens LA, et al.: Cyclophosphamide, doxorubicin and paclitaxel enhance the antitumor immune response of granulocyte-macrophage colony-stimulating factor-secreting whole cell vaccines in Her-2/neu tolerized mice. Cancer Res 2001, 61:3689-3697. Demonstrates that ess response occurs to a GM-CSF tumor cell-based vaccine in an immune tolerant transgenic murine model as compared with nontransgenic model. Also, the authors demonstrate an enhancement of vaccine efficacy when administered with combination chemotherapy of cyclophosphamide and doxorubic n on an immunomodulating schedule.
52. Mitchell MS, Kan-Mitchell J, Kempf RA, et al.: Active specific immunotherapy for melanoma: Phase I trial of allogeneic lysate and a novel adjuvant. Cancer Res 1998, 48:5883-5893.
53. Elliott GT, McLeod RA, Perez J, et al.: Interim results of a phase II multi-center clinical trial evaluating the activity of a therapeutic allogeneic melanoma vaccine (theraccine) in the treatment of disseminated malignant melanoma. Semin Surg Oncol 1993, 2:41-53.
54. Harel W, Goedegebuure PS, LeMay LG, et al.: Melanoma specific lysis by cloned CD4+ and CD8+ T cells from actively immunized melanoma patients. Vaccine Res 1993, 2:41-53
55. Sondak VK, Liu PY, Tuthill RJ, et al.: Adjuvant immunotherapy of resected intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: Overall results of a randomized trial of Southwest Oncology Group. J Clin Oncol 2002, 20:2058-2066. Presents findings from a major randomized cooperative group study of tumorlysate vaccine for intermediate thickness, node-negative melanoma. Despite an earlier analysis suggesting an improved disease-free survival, therapy with 2 year of this allogeneic tumorlysate vaccine had no benefit over observation.
56. Steinman RM: The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 1991, 9:271-296.
57. Inaba K, Witmer-Pack M, Inaba M, et al.: The tissue distribution of the B7-2 costimulator in mice: Abundant expression on dendritic cells in situ and during maturation in vitro. J Exp Med 1994, 180:1849-1860.
58. Young JW, Steinman RM: The hematopoetic development of dendritic cells: A distinct pathway for myeloid differentiation. Stem Cells 1996, 14:376-387.
59. Sertl K, Takemura T, Tsachachler E, et al.: Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma and visceral pleura. J Exp Med 1986, 163:463-451.
60. Inaba K, Inaba M, Romani N, et al.: Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 1992, 1693-1702.
61. Caux C, Vanbervliet B, Massacrier C, et al.: CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF + TNF alpha. J Exp Med 1996, 184:695-706.
62. Szabolcs P, Moore MA, Young JW: Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured with c-kit ligand, granulocyte-macrophage colony-stimulating factor and TNF-alpha. J Immunol 1995, 154:5851-5861.
63. O'Doherty U, Pen M, Gezetter S, et al.: Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. Immunology 1994, 82:487-493.
64. Kampgen E, Koch F, Heufler C, et al.: Understanding the dendritic cell lineage through a study of cytokine receptors. J Exp Med 1994, 179:1767-1776.
65. Santiago-Swartz F, Divaris N, Kay C, et al.: Mechanisms of tumor necrosis factor-granulocyte-macrophage colony-stimulating factor induced dendritic cell development. Blood 1993, 82:3019-3028.
66. Flores-Romo L, Bjorck P, Duvert V, et al.: CD40 ligation on human cord blood CD34 progenitors induces proliferation and differentiation into functional dendritic cells. J Exp Med 1997, 185:341-349.
67. Askew D, Chu RS, Kreig AM, et al.: CpG DNA induces maturation of dendritic cells with distinct effects on nascent and recycling MHC II antigen processing mechanisms. J Immunol 2000, 165:6889-6895.
68. Bullock TN, Colella TA, Engelhard VH.: The density of peptides displayed by dendritic cells affects immune responses to human tyrosinase and gp100 in HLA-A2 transgenic mice. J Immunol 2000, 164:2354-2361.
69. Mayordomo JI, Zorina T, Storkus WJ, et al.: Bone-marrow derived dendritic cells pulsed with synthetic tumor peptides elicit protective and therapeutic anti-tumor immunity. Nat Med 1995, 1:1297-1302.
70. Zitvogel L, Mayordomo JI, Tjandrawan T, et al.: Therapy of murine tumors with tumor peptide-pulsed dendritic cells: Dependence on T cells, B7costimulation and T helper cell 1 associated cytokines. J Exp Med 1996, 183:87-97.
71. Wang RF, Wang HY: Enhancement of antitumor immunity by prolonging antigen presentation on dendritic cells. Nature Biotech 2002, 20:149-154.
72. Nestle FO, Alijacic S, Gilliet M, et al.: Vaccination of melanoma patients with peptide or tumor lysate pulsed dendritic cells. Nat Med 1998, 4:328-332.
73. Yu JS, Wheeler CJ, Zeltzer PM, et al.: Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T cell infiltration. Cancer Res 2001, 61:842-847.
74. Banchereau J, Plauka AK, Dhodapkar M, et al.: Immune and clinical responses in patients with metastatic melanoma to CD34+ progenitor-derived dendritic cell-vaccine. Cancer Res 2001, 61:6451-6458.
75. Fong L, Brockstedt D, Benike C, et al.: Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy. J Immunol 2001, 167:7150-7156.
76. Zaks TZ, Rosenberg SA: Immunization with a peptide epitope (p369-377) from Her 2 neu leads to peptide-specific cytotoxic T lymphocytes that fail to recognize Her2/neu+ tumors. Cancer Res 1998, 58:4902-4908.
77. Hoffman TK, Nakano K, Elder EM, et al.: Generation of T cells specific for the wild-type sequence p53(264-272) peptide in cancer patients: Implications for immunoselection of epitope loss variants. J Immunol 2000, 165:5938-5944.
78. Timmerman JM, Czerwinski DK, Davis TA, et al.: Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: Clinical and immune responses in 35 patients. Blood 2002, 99:1517-1526.
79. Ashley DM, Faiola B, Nair S, et al.: Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors. J Exp Med 1997, 186:1177-1182.
80. Boczkowski D, Nair SK, Synder D, Gilboa E: Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 1996, 184:465-472.
81. Heiser A, Coleman D, Dannull J, et al.: Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. J Clin Invest 2002, 109:409-417.
82. Wan Y, Branson J, Pilon A, et al.: Genetically modified dendritic cells prime autoreactive T cells through a pathway independent of CD40L and interleukin-12: Implications for cancer vaccines. Cancer Res 2000, 60:3247-3253.
83. Brown M, Zhang Y, Dermine S, et al.: Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity. Gene Ther 2000, 7:1680-1689.
84. Yang S, Kittlesen D, Slingluff CL, et al.: Dendritic cells infected with a vaccinia vector carrying the human GP100 gene simultaneously present multiple epitopes and restricted by HLA-A2 and A3. J Immunol 2000, 164:4204-4211.
85. Zhu M, Terasawa H, Gulley J, et al.: Enhanced activation of human T cells via avipox vector-mediated hyper-expression of a triad of costimulatory molecules in human dendritic cells. Cancer Res 2001, 61:3725-3734. The use of avipox vector carrying a tricistronic transgene for three major co-stimulatory molecules is used to transduce dendritic cells and shown to enhance the number of cells expressing these molecules, the qualitative level of expression, and the tumor specific killing when the DC are also pulsed with tumor antigen. Blocking of any one of three co-stimulatory molecules abrogates part or all of its effect. This strategy is interesting given the variability of co-stimulatory molecule expression seen on DC from patients with cancer.
86. Hodge JW, Rad AN, Grosenbach DW, et al.: Enhanced T cell activation by dendritic cells engineered to hyper-express a triad of costimulatory molecules. J Natl Cancer Inst 2000, 92:1228-1239.
87. Dynall J, Latouche JB, Schnell S, et al.: Lentivirus transduced human monocyte-derived dendritic cells efficiently stimulate antigen-specific cytotoxic lymphocytes. Blood 2001, 97:114-121. The authors described the construction of a rovel lentiviral vectro derived from the human immunodeficiency virus backbone. The vector can readily transduce both immature and mature myeloid-derived DC as well as monocyte-derived DC with 35% efficiency, which is substantially higher to their comparative results seen with a standard murine leukemia-derived retroviral vector.
88. Mangeot PE, Negre D, Dubios B, et al.: Development of minimal lentivirus vectors derived from simian immunodeficiency virus (SIVmac251) and their use for gene transfer into human dendritic cells. J Virol 2000, 74:8307-8315. Describes a novel lentiviral constructed from Simian immunodeficiency virus and its subsequent ability to transduce 40% of DC, including monocyte-derived and terminally matured, nondividing myeloid derived DC.
89. Motta I, Andre F, Lim A, et al.: Cross-presentation by dendritic cells of tumor antigen expressed in apoptotic recombinant canary-pox virus-infected dendritic cells. J Immunol 2001, 167:1795-1802. An interestingly report on use of canary-pox infected DC as a source of antigen for immature DC as a means of cross-presenting Ag. The immature DC subsequently express tumor antigen and evoke tumor-specific CTL with increased IFN-γ production as compared with vector-transduced or peptide-pulsed DC.
90. Ignatius R, Marovich M, Mehlhop E, et al. Canary virus-induced maturation of dendritic cells is mediated by apoptotic cell death and tumor necrosis factor alpha secretion. J Virol 2000, 74:11329-11338.
91. Herr W, Ranieri E, Olson W, et al.: Mature dendritic cells pulsed with freeze-thaw lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4+ and CD8+ T lymphocyte responses. Blood 2000, 96:1857-1864.
92. Shimizu K, Thomas EK, Giedlin M, et al.: Enhancement of tumor-lysate- and peptide-pulsed dendritic cell-based vaccines by the addition of foreign helper protein. Cancer Res 2001, 61:2618-2624.
93. Geiger JD, Hutchinson RJ, Honenkirk LF, et al.: Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res 2001, 61:8513-8519.
94. Russo V, Tanzarella S, Dalerba P, et al.: Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class-I restricted T cell response. Proc Natl Acad Sci USA 200, 97:2185-2190.
95. Albert ML, Sauter B, Bardwaj N.: Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998, 392:86-89.
96. Albert ML, Peearce SF, Francisco CM, et al.: Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross present antigens to cytotoxic T lymphocytes. J Exp Med 1998, 188:1359-1368.
97. Sauter B, Albert ML, Francisco L, et al.: Consequences of cell death: Exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 2000, 191:423-434.
98. Gong J, Chen D, Kashiwaba M, et al.: Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells. Proc Natl Acad Sci USA 1998, 95:6279-6283.
99. Celluzi CM, Falo LD: Physical interaction between dendritic cells and tumor cells results in an immunogen that induces protective and therapeutic tumor rejection. J Immunol 1998, 160:3082-3085.
100. Lespagnard L, Mettens P, Verheyden AM, et al.: Dendritic cells fused with mastocytoma cells elicit therapeutic antitumor immunity. Int J Cancer 1998, 76:250-258.
101. Wang J, Saffold S, Cao X, et al. Eliciting T cell Immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol 1998, 161:5516-5524.
102. Gong J, Avigan D, Chen D, et al.: Initiation of antitumor cytotoxic T lymphocytes by fusions of human DC and breast carcinoma cells. Proc Natl Acad Sci USA 2000. 97:2715-2718.
103. Gong J, Nikrui N, Chen D, et al.: Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol 2000, 165:1705-1711.
104. Kugler A, Stuler G, Walden P, et al.: Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med 2000, 6:332-336.
105. Morse MA, Clay TM, Hobeika AC, et al.: Surrogate markers of response to cancer immunotherapy. Expert Opin Biol Ther 2001, 1:153-158.
106. Simon RM, Steinberg SN, Hamilton M, et al. Clinical trial designs for the early clinical development of therapeutic cancer vaccines. J Clin Oncol 2001, 19:1848-1854. An overview of the clinical trial design challenges for cancer vaccine protocols. The authors outline the need for a different paradigm for these unique therapies and pose suggestions on improving the ongoing research efforts to maximize the ablility to detect an efficacious strategy.