Tumor vaccines for breast cancer

Cancer Investigation

Volumn 27, Issue 4, 2009, Pages 361-368

  Anderson, Karen S ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

'TRICOM'; B LYMPHOCYTE ANTIBODY; CANCER VACCINE; CARCINOEMBRYONIC ANTIGEN; CISPLATIN; CPG OLIGODEOXYNUCLEOTIDE; CYCLOPHOSPHAMIDE; CYTOCHROME P450 1B1; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; DENDRITIC CELL VACCINE; DENILEUKIN DIFTITOX; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FLUOROURACIL; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IMMUNOLOGICAL ADJUVANT; INDOLEAMINE 2,3 DIOXYGENASE; INDOLEAMINE 2,3 DIOXYGENASE INHIBITOR; INTERLEUKIN 10; IPILIMUMAB; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MUCIN 1; NATURAL KILLER CELL RECEPTOR NKG2D; PACLITAXEL; QS 21; TELOMERASE; TOLL LIKE RECEPTOR AGONIST; TRASTUZUMAB; TRIPLE VACCINE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CYTOKINE; TERT PROTEIN, HUMAN; TUMOR ANTIGEN;

ADAPTIVE IMMUNITY; ADOPTIVE IMMUNOTHERAPY; ALLOGENEIC STEM CELL TRANSPLANTATION; ANTIBODY RESPONSE; ANTIGEN PRESENTATION; ANTIGEN RECOGNITION; AUTOIMMUNITY; B LYMPHOCYTE; BREAST CANCER; BREAST CARCINOMA; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CD4+ CD25+ T LYMPHOCYTE; CHRONOTHERAPY; COLON CANCER; CYTOKINE RELEASE; DENDRITIC CELL; DONOR LYMPHOCYTE INFUSION; DRUG EFFECT; DRUG POTENTIATION; DRUG TARGETING; HUMAN; IMMUNOGENICITY; IMMUNOLOGICAL MEMORY; IMMUNOREGULATION; INNATE IMMUNITY; KIDNEY CARCINOMA; LEUKAPHERESIS; LYMPH NODE METASTASIS; LYMPHOCYTE DEPLETION; LYMPHOCYTE FUNCTION; LYMPHOCYTE MIGRATION; MACROPHAGE; MAJOR HISTOCOMPATIBILITY COMPLEX; MELANOMA; NATURAL KILLER CELL; NONHUMAN; OVARY CANCER; OVARY CARCINOMA; PRIORITY JOURNAL; PROSTATE CANCER; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE; TUMOR IMMUNITY; ANIMAL; ANTIBODY PRODUCTION; BREAST TUMOR; CELLULAR IMMUNITY; FEMALE; IMMUNIZATION; IMMUNOLOGY; METABOLISM; VACCINATION;

ANIMALS; ANTIBODY FORMATION; ANTIGEN PRESENTATION; ANTIGENS, NEOPLASM; BREAST NEOPLASMS; CANCER VACCINES; CYTOKINES; DENDRITIC CELLS; FEMALE; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, INNATE; IMMUNIZATION SCHEDULE; IMMUNOLOGIC MEMORY; MUCIN-1; RECEPTOR, ERBB-2; T-LYMPHOCYTES; TELOMERASE; VACCINATION;

EID: 65249154941     PISSN: 07357907     EISSN: 15324192     Source Type: Journal    
DOI: 10.1080/07357900802574421     Document Type: Review

References (115)

1. Chaudhuri, S.; Cariappa, A.; Tang, M.; et al. Genetic susceptibility to breast cancer: HLA DQB03032 and HLA DRB111 may represent protective alleles. Proc Natl Acad Sci USA 2000, 97, 11451-11454.
2. Marincola, F.M.; Jaffee, E.M.; Hicklin, D.J.; etai. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 2000, 74,181-273.
3. Campoli, M.; Chang, CC; Oldford, SA.; et al. HLA antigen changes in malignant tumors of mammary epithelial origin: molecular mechanisms and clinical implications. Breast Dis 2004, 20, 105-125.
4. Aaltomaa, S.; Lipponen, P.; Eskelinen, M.; et al. Lymphocyte infiltrates as a prognostic variable in female breast cancer. Eur J Cancer 1992, 28A, 859-864.
5. Menard, S.; Tomasic, G.; Casalini, P.; et al. Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res 1997, 3, 817-819.
6. Jerome, K.R.; Domenech, N.; Finn, O.J. Tumor-specific cytotoxic T -cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA. J Immunol 1993, 151, 1654-1662.
7. Disis, M.L.; Calenoff, E.; McLaughlin, G.; et al. Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 1994, 54,16-20.
8. Bishop, M.R.; Fowler. D.H.; Marchigiani, D.; et al. Allogeneic lymphocytes induce tumor reg0ression of advanced metastatic breast cancer. J Clin Oncol 2004, 22, 3886-3892.
9. Lundqvist, A.; Childs, R. Allogeneic hematopoietic cell transplantation as immunotherapy for solid tumors: current status and future directions. J Immunother 2005, 28, 281-288.
10. Carella, A.M.; Beltrami, G.; Corsetti, M.T.; et al. Reduced intensity conditioning for allograft after cytoreductive autograft in metastatic breast cancer. Lancet 2005, 366, 318- 320.
11. Janeway, C.T.R; Walport, M.; Shlomchikm M. Immunobiology: The Immune System in Health and Disease. 6th ed. New York, NY: Garland Science Publishing, 2005.
12. Iwasaki, A.; Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004, 5, 987-995.
13. Vollmer, J. Progress in drug development of immunostimulatory CpG oligodeoxynucleotide ligands for TLR9. Expert Opin Biol Ther 2005, 5, 673-682.
14. Speiser, D.E.; Lienard, D.; Rufer, N.; et al. Rapid and strong human CD8+ T cell responses to vaccination with peptide, I FA, and CpG oligodeoxynucleotide 7909. J Clin Invest 2005, 115, 739- 746.
15. Diefenbach, A.; Raulet, D.H. The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol Rev 2002, 188, 9-21.
16. Smyth, M.J.; Swann, J.; Cretney, E.; et al. NKG2D function protects the host from tumor initiation. J Exp Med 2005, 202, 583- 588.
17. Bauer, S.; Groh, V.; Wu, J.; et al. Activation of NK cells and Tcells by NKG2D, a receptor for stress-inducible MICA. Science 1999, 285, 727-729.
18. Groh, V.; Rhinehart, R.; Secrist, H.; etal. Broad tumor-associated expression and recognition by tumor-derived gamma delta Tcells of MICA and MICB. Proc Natl Acad Sci USA 1999, 96, 6879- 6884.
19. Groh, V.; Wu, J.; Yee, C; et al. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature2002, 419, 734-738.
20. Singer, G.; Rebmann, V.; Chen, Y.C.; et al. HLA-G is a potential tumor marker in malignant ascites. Clin Cancer Res 2003, 9, 4460-4464.
21. Zaks, T.Z.; Rosenberg, S.A. Immunization with a peptide epitope (p369-377) from HER-2/neu leads to peptide-specific cytotoxic T lymphocytes that fail to recognize HER-2/neu+ tumors. Cancer Res 1998, 58, 4902-4908.
22. Vonderheide, R.H.; Hahn, W.C.; Schultze, J.L; et al. The telom- erase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 1999, 10, 673-679.
23. Maecker, B.; Sherr, D.H.; Vonderheide, R.H.; et al. The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells. Blood 2003, 102, 3287- 3294.
24. Kao, H.; Marto, J.A.; Hoffmann, T.K.; et al. Identification of cy- clin B1 as a shared human epithelial tumor-associated antigen recognized by T cells. J Exp Med 2001, 194,1313-1323.
25. Khong, H.T.; Yang, J.C.; Topalian, S.L.; et al. Immunization of HLA-A.0201 and/or HLADPbeta104 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen. J Immunother 2004, 27, 472-477.
26. Salazar, L.G.; Fikes, J.; Southwood, S.; et al. Immunization of cancer patients with HER-2/neu-derived peptides demonstrating high-affinity binding to multiple class II alleles. Clin Cancer Res2003, 9, 5559-5565.
27. Anderson, K.S.; LaBaer, J. The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res 2005, 4, 1123-1133.
28. MacLean, G.D.; Miles, D.W.; Rubens, R.D.; et al. Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide. J Immunother Emphasis Tumor Immunol 1996, 19, 309-316.
29. Sandmaier, B.M.; Oparin, D.V.; Holmberg, LA.; et al. Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue, and immunization with Theratope STn-KLH cancer vaccine. J Immunother 1999, 22, 54-66.
30. Holmberg, LA.; Oparin, D.V.; Gooley, T.; et al. Clinical outcome of breast and ovarian cancer patients treated with high-dose chemotherapy, autologous stem cell rescue and THERATOPE STn-KLH cancer vaccine. Bone Marrow Transplant 2000, 25, 1233-1241.
31. Musselli, C; Livingston, P.O.; Ragupathi, G. Keyhole limpet hemocyanin conjugate vaccines against cancer: the Memorial Sloan Kettering experience. J Cancer Res Clin Oncol 127 Suppl 2001,2, R20-R26.
32. Disis, M.L.; Pupa, S.M.; Gralow, J.R.; et al. High-titer HER-2/neu protein-specific antibody can be detected in patients with early- stage breast cancer. J Clin Oncol 1997, 15, 3363-3367.
33. Stockert, E.; Jager, E.; Chen, Y.T.; et al. A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. J Exp Med 1998, 187,1349-1354.
34. Sioud, M.; Hansen, M.H. Profiling the immune response in patients with breast cancer by phage-displayed cDNA libraries. Eur J Immunol 2001, 31, 716-725.
35. Sugita, Y; Wada, H.; Fujita, S.; et al. NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors. Cancer Res 2004, 64,2199-2204.
36. Wang, X.; Yu, J.; Sreekumar, A.; et al. Autoantibody signatures in prostate cancer. N Engl J Med 2005, 353,1224-1235.
37. Hodi, F.S.; Schmollinger, J.C.; Soiffer, R.J.; et al. ATP6S1 elicits potent humoral responses associated with immune-mediated tumor destruction. Proc Natl Acad Sci USA 2002, 99,6919-6924.
38. Gnjatic, S.; Atanackovic, D.; Jager, E.; et al. Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses. Proc Natl Acad Sci USA 2003, 100, 8862-8867.
39. Zou, W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 2005, 5, 263- 274.
40. Zou, W.; Machelon, V.; Coulomb-L'Hermin, A.; et al. Stromal- derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 2001, 7, 1339-1346.
41. Rollins, B.J. Inflammatory chemokines in cancer growth and progression. Eur J Cancer 2006, 42, 760-767.
42. Greenwald, R.J.; Freeman, G.J.; Sharpe, A.H. The B7 family revisited. Annu Rev Immunol 2005, 23, 515-548.
43. Muschen, M.; Moers, C; Warskulat, U.; et al. CD95 ligand expression as a mechanism of immune escape in breast cancer. Immunology 2000, 99, 69-77.
44. Brown, J.A.; Dorfman, D.M.; Ma, F.R.; et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 2003, 170, 1257- 1266.
45. Tringler, B.; Zhuo, S.; Pilkington, G.; et al. B7-h4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res 2005, 11,1842-1848.
46. Schuler, G.; Schuler-Thurner, B.; Steinman, R.M. The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 2003,15, 138-147.
47. Wilcox, R.A.; Tamada, K.; Flies, D.B.; et al. Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo. Blood 2004, 103,177-184.
48. Bansal-Pakala, P.; Jember, A.G.; Croft, M. Signaling through OX40 (CD134) breaks peripheral T-cell tolerance. Nat Med 2001, 7,907-912.
49. O'Neill, D.W.; Adams, S.; Bhardwaj, N. Manipulating dendritic cell biology for the active immunotherapy of cancer. Blood 2004, 104, 2235-2246.
50. Gervais, A.; Leveque, J.; Bouet-Toussaint, F.; et al. Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency. Breast Cancer Res 2005, 7, R326-R335.
51. Munn, D.H.; Sharma, M.D.; Lee, J.R.; et al. Potential regulatory function of human dendritic cells expressing indoleamine 2,3- dioxygenase. Science 2002, 297,1867-1870.
52. Mellor, A.L.; Munn, D.H. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004, 4, 762-774.
53. Nair, S.K.; Morse, M.; Boczkowski, D.; et al. Induction of tumor- specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells. Ann Surg 2002,235,540- 549.
54. Nestle, F.O.; Alijagic, S.; Gilliet, M.; etal. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998, 4, 328-332.
55. Avigan, D.; Vasir, B.; Gong, J.; et al. Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res 2004, 10,4699- 4708.
56. Holtl, L.; Zelle-Rieser, C; Gander, H.; et al. Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 2002, 8, 3369-3376.
57. O'Rourke, M.G.; Johnson, M.; Lanagan, C; et al. Durable complete clinical responses in a phase l/ll trial using an autologous melanoma cell/dendritic cell vaccine. Cancer Immunol Im- munother 2003, 52, 387-395.
58. Small, E.J.SPR; Higano, C; Neumanaitis, J.; Valone, F.; Her- schberg, R.M. Immunotherapy (APC8015) for androgen independent prostate cancer (AIPC): Final survival data from a phase 3 randomized placebo-controlled trial, 2005 ASCO Prostate Cancer Symposium, 2005.
59. Morse, M.A.; Clay, T.M.; Hobeika, A.C.; et al. Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. Clin Cancer Res 2005, 11,3017-3024.
60. Morse, M.A.; Nair, S.K.; Mosca, P.J.; et al. Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA. Cancer Invest 2003, 21, 341-349.
61. Brossart, P.; Wirths, S.; Stuhler, G.; et al. Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide- pulsed dendritic cells. Blood 2000, 96, 3102-3108.
62. Wobser, M.; Keikavoussi, P.; Kunzmann, V.; et al. Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin. Cancer Immunol Immunother 2006, 55, 1294-1298.
63. Otto, K.; Andersen, M.H.; Eggert, A.; et al. Lack of toxicity of therapy-induced T cell responses against the universal tumour antigen survivin. Vaccine 2005, 23, 884-889.
64. Taylor-Papadimitriou, J.; Finn, O.J. Biology, biochemistry and immunology of carcinomaassociated mucins. Immunol Today 1997, 18,105-107.
65. Goydos, J.S.; Elder, E.; Whiteside, T.L.; et al. A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma. J Surg Res 1996, 63, 298-304.
66. Reddish, M.; MacLean, G.D.; Koganty, R.R.; et al. Anti-MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide. Int J Cancer 1998, 76, 817-823.
67. Gilewski, T.; Adluri, S.; Ragupathi, G.; et al. Vaccination of high- risk breast cancer patients with mucin-1 (MUC1) keyhole limpet hemocyanin conjugate plus QS-21. Clin Cancer Res 2000, 6, 1693-1701.
68. Karanikas, V; Thynne, G.; Mitchell, R; et al. Mannan Mucin-1 Peptide Immunization: Influence of Cyclophosphamide and the Route of Injection J Immunother 2001, 24,172-183.
69. Snijdewint, F.G.; von Mensdorff-Pouilly, S.; Karuntu-Wanamarta, A.H.; et al. Antibodydependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients. Int J Cancer 2001, 93, 97-106.
70. Karanikas, V; Hwang, L.A.; Pearson, J.; et al. Antibody and Tcell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein. J Clin Invest 1997, 100, 2783- 2792.
71. Murray, J.L; Gillogly, M.E.; Przepiorka, D.; etal. Toxicity, immuno- genicity, and induction of E75-specific tumor-lytic CTLs by HER-2 peptide E75 (369-377) combined with granulocyte macrophage colony-stimulating factor in HLA-A2+ patients with metastatic breast and ovarian cancer. Clin Cancer Res 2002, 8,3407-3418.
72. Knutson, K.L.; Schiffman, K.; Cheever, M.A.; et al. Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity. Clin Cancer Res 2002, 8, 1014-1018.
73. Disis, M.L.; Gooley, T.A.; Rinn, K.; et al. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J. Clin. Oncol. 2002, 20, 2624-2632.
74. Knutson, K.L.; Schiffman, K.; Disis, M.L. Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients. J Clin Invest 2001, 107, 477- 484.
75. Disis, M.L.; Schiffman, K.; Guthrie, K.; et al. Effect of dose on immune response in patients vaccinated with an her-2/neu intracellular domain protein-based vaccine. J Clin Oncol 2004, 22, 1916-1925.
76. Morse, M.A.; Clay, T.M.; Colling, K.; et al. HER2 dendritic cell vaccines. Clin Breast Cancer 3 Suppl 2003, 4, S164-S172.
77. Peoples, G.E.; Gurney, J.M.; Hueman, M.T.; et al. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. J Clin Oncol 2005, 23, 7536- 7545.
78. Vonderheide, R.H.; Domchek, S.M; Schultze, J.L; et al. Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res 2004, 10,828- 839.
79. Su, Z.; Dannull, J.; Yang, B.K.; et al. Telomerase mRNA- transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J Immunol 2005, 174, 3798-3807.
80. Parkhurst, M.R.; Riley, J.P.; Igarashi, T.; et al. Immunization of patients with the hTERT:540-548 peptide induces peptide-reactive T lymphocytes that do not recognize tumors endogenously expressing telomerase. Clin Cancer Res 2004, 10,4688-4698.
81. Ho, W.Y.; Blattman, J.N.; Dossett, M.L; et al. Adoptive immunotherapy: engineering T cell responses as biologic weapons for tumor mass destruction. Cancer Cell 2003, 3, 431-437.
82. Mach, N.; Dranoff, G. Cytokine-secreting tumor cell vaccines. Curr Opin Immunol 2000, 12, 571-575.
83. Ahlert, T; Sauerbrei, W.; Bastert, G.; et al. Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer. J Clin Oncol 1997, 15, 1354-1366.
84. Wood, G.; Baynes, R. Vaccination of Stage IV Breast Cancer Patients with Whole Autologous Malignant Cells and Granulocyte Mactrophage Colony Stimulating Factor. Proc Am Soc Clin Oncol 1999 [abstr 168].
85. Dillman, R.O.; Beutel, L.D.; Barth, N.M.; et al. Irradiated cells from autologous tumor cell lines as patient-specific vaccine therapy in 125 patients with metastatic cancer: induction of delayed- type hypersensitivity to autologous tumor is associated with improved survival. Cancer Biother Radiopharm 2002, 17, 51- 66.
86. Wiseman, C.L. Inflammatory breast cancer. 10-year follow-up of a trial of surgery, chemotherapy, and allogeneic tumor cell/BCG immunotherapy. Cancer Invest 1995, 13, 267-271.
87. Schoof, D.D.; Smith, J.W.; II; Disis, M.L.; et al. Immunization of metastatic breast cancer patients with CD80-modified breast cancer cells and GM-CSF. Adv Exp Med Biol 1998, 451, 511- 518.
88. Jiang, X.P.; Yang, D.C.; Elliott, R.L.; et al. Vaccination with a mixed vaccine of autogenous and allogeneic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125-results in immune and clinical responses in breast cancer patients. Cancer Biother Radiopharm 2000, 15, 495-505.
89. Avigan, D. Fusions of breast cancer and dendritic cells as a novel cancer vaccine. Clin Breast Cancer 3 Suppl 2003,4, S158- S163.
90. Dranoff, G.; Jaffee, E.; Lazenby, A.; et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte- macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993, 90, 3539-3543.
91. Wang, R.F. Functional control of regulatory T cells and cancer immunotherapy. Semin Cancer Biol 2006, 16,106-114.
92. Khazaie, K.; von Boehmer, H. The impact of CD4(+)CD25(+) Treg on tumor specific CD8(+) T cell cytotoxicity and cancer. Semin Cancer Biol 2006, 16,124-136.
93. Liyanage, U.K.; Moore, T.T.; Joo, H.G.; et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microen- vironment of patients with pancreas or breast adenocarcinoma. J Immunol 2002, 169, 2756-2761.
94. DeLong, P.; Carroll, R.G.; Henry, A.C.; et al. Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma. Cancer Biol Ther 2005, 4, 342- 346.
95. Curiel, T.J.; Coukos, G.; Zou, L; et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004, 10, 942-949.
96. Dannull, J.; Su, Z.; Rizzieri, D.; et al. Enhancement of vaccine- mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 2005, 115, 3623-3633.
97. Barnett, B.; Kryczek, I.; Cheng, P.; et al. Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am J Reprod Immunol 2005, 54, 369-377.
98. Waterhouse, P.; Penninger, J.M.; Timms, E.; et al. Lymphopro- liferative disorders with early lethality in mice deficient in Ctla-4. Science 1995, 270, 985-988.
99. Tivol, E.A.; Borriello, F.; Schweitzer. A.N.; et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA- 4. Immunity 1995, 3, 541-547.
100. Leach, D.R.; Krummel, M.F.; Allison, J.R Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996, 271,1734- 1736.
101. Hodi, F.S.; Mihm, M.C.; Soiffer, R.J.; et al. Biologic activity of cytotoxic T lymphocyteassociated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA 2003, 100, 4712- 4717.
102. Ribas, A.; Camacho, L.H.; Lopez-Berestein, G.; et al. Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol 2005, 23, 8968-8977.
103. Phan, G.Q.; Yang, J.C.; Sherry, R.M.; et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 2003, 100, 8372-8377.
104. Sanderson, K,; Scotland, R.; Lee, P.; et al. Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen- 4 monoclonal antibody with multiple melanoma peptides and Montanide ISA 51 for patients with resected stages III and IV melanoma. J Clin Oncol 2005,23, 741-750.
105. Davis, T.A.T.S.; Korman, A.; etal. MDX-010 (human anti-CTLA4): a phase 1 trial in hormone refractory prostate carcinoma (HRPC), Proc Am Soc Clin Oncol 2002, 21, 2002 (abstr 74).
106. Attia, P.; Phan, G.Q.; Maker, A.V.; et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 2005, 23, 6043-6053.
107. Hodi, F.S.; Seiden, M.; Butler, M.; et al. Cytotoxic T lymphocyte- associated antigen-4 (CTLA-4) antibody blockade in patients previously vaccinated with irradiated, autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF). J Clin Oncol 2004. ASCO Annual Meeting Proceedings 2004, 22(145), 2536.
108. Perou, CM.; Sorlie, T.; Eisen, M.B.; et al. Molecular portraits of human breast tumours. Nature 2000, 406, 747-752.
109. Porter, D.A.; Krop, I.E.; Nasser, S.; et al. A SAGE (serial analysis of gene expression) view of breast tumor progression. Cancer Res 2001, 61, 5697-5702.
110. Altman, J.D.; Moss, P.A.; Goulder, P.J.; etal. Phenotypicanalysis of antigen-specific T lymphocytes. Science 1996, 274, 94-96.
111. Emens, L.A.; Jaffee, E.M.; Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Res 2005, 65, 8059- 8064.
112. Yang, S.; Haluska, F.G. Treatment of melanoma with 5-fluorouracil or dacarbazine in vitro sensitizes cells to antigen-specific CTL lysis through perforin/granzyme- and Fasmediated pathways. J Immunol 2004, 172, 4599-4608.
113. Keane, M.M.; Ettenberg, S.A.; Nau, M.M. et al. Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. Cancer Res 1999, 59,734-741.
114. Lutsiak, M.E.; Semnani, R.T.; De Pascalis, R.; et al. Inhibition of CD4(+)25-l- Tregulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 2005, 105, 2862-2868.
115. Gribben, J.G.; Ryan, D.P.; Boyajian, R.; et al. Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin Cancer Res 2005, 11, 4430-4436.