Breast cancer vaccines: Ongoing national cancer institute-registered clinical trials

Expert Review of Vaccines

Volumn 10, Issue 6, 2011, Pages 755-774

  Mittendorf, Elizabeth A ^a   Alatrash, Gheath ^a   Xiao, Haile ^a   Clifton, G Travis ^b   Murray, James L ^a   Peoples, George E ^b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b BROOKE ARMY MEDICAL CENTER   (United States)

Author keywords

breast cancer; clinical trials; immunotherapy; vaccines

Indexed keywords

AE 37 PEPTIDE; ANTINEOPLASTIC AGENT; CANCER VACCINE; CYCLOPHOSPHAMIDE; DENDRITIC CELL VACCINE; DOCETAXEL; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EXEMESTANE; GP2 PEPTIDE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HLA A2 ANTIGEN; LARGE MULTIVALENT IMMUNOGEN VACCINE; NAVELBINE; PACLITAXEL; PANVAC; PANVAC F; PANVAC V; PEPTIDE VACCINE; PROTEIN P53; RECOMBINANT GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; RECOMBINANT HORMONE; RECOMBINANT INTERLEUKIN 2; TAXANE DERIVATIVE; THYMAFSIN; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRUS VACCINE; VIRUS VECTOR; WHOLE TUMOR CELL VACCINE;

ADJUVANT THERAPY; ANTIGEN PRESENTING CELL; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER GROWTH; CANCER RADIOTHERAPY; CANCER REGISTRY; CANCER STAGING; CANCER SURGERY; CELL PROLIFERATION; CELLULAR IMMUNITY; CYTOTOXIC T LYMPHOCYTE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; EVENT FREE SURVIVAL; GENE OVEREXPRESSION; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; IMMUNOHISTOCHEMISTRY; IMMUNOLOGICAL TOLERANCE; LOW DRUG DOSE; MELANOMA; METASTASIS; NONHUMAN; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); POXVIRUS; PRIORITY JOURNAL; PROGNOSIS; PROGRESSION FREE SURVIVAL; PROTEIN FUNCTION; REVIEW; T LYMPHOCYTE; VACCINIA VIRUS;

BREAST NEOPLASMS; CANCER VACCINES; CLINICAL TRIALS, PHASE II AS TOPIC; FEMALE; HUMANS; NATIONAL CANCER INSTITUTE (U.S.); TREATMENT OUTCOME; UNITED STATES;

EID: 79959552163     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/erv.11.59     Document Type: Review

References (101)

1. Burch PA, Breen JK, Buckner JC et al. Priming tissue-specific cellular immunity in a Phase I trial of autologous dendritic cells for prostate cancer. Clin. Cancer Res. 6(6), 2175-2182 (2000 (Pubitemid 30399182)
2. Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363(5), 411-422 (2010
3. Gianni L, Dafni U, Gelber RD et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 12(3), 236-244 (2011
4. Piccart-Gebhart MJ, Procter M, Leyland- Jones B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 353(16), 1659-1672 (2005 (Pubitemid 41464705)
5. Romond EH, Perez EA, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 353(16), 1673-1684 (2005 (Pubitemid 41464706)
6. Robson NC, Hoves S, Maraskovsky E, Schnurr M. Presentation of tumour antigens by dendritic cells and challenges faced. Curr. Opin. Immunol. 22(1), 137-144 (2010
7. Mittendorf EA, Czerniecki BJ, Peoples GE. Breast Cancer Vaccines. In: Kuerer's Breast Surgical Oncology. Henry Kuerer (Ed.McGraw-Hill, New York, NY, USA, 937-945 (2010
8. Emens LA. Cancer vaccines: on the threshold of success. Expert Opin. Emerg. Drugs 13(2), 295-308 (2008 (Pubitemid 351957349)
9. Satthaporn S, Robins A, Vassanasiri W et al. Dendritic cells are dysfunctional in patients with operable breast cancer. Cancer Immunol. Immunother 53(6), 510-518 (2004 (Pubitemid 38680257)
10. Dees EC, McKinnon KP, Kuhns JJ et al. Dendritic cells can be rapidly expanded ex vivo and safely administered in patients with metastatic breast cancer. Cancer Immunol. Immunother. 53(9), 777-785 (2004 (Pubitemid 39149904)
11. Slamon DJ, Clark GM, Wong SG et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science (New York NY) 235(4785), 177-182 (1987 (Pubitemid 17231334)
12. Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244(45), 707-712 (1989 (Pubitemid 19147683)
13. Fisk B, Blevins TL, Wharton JT, Ioannides CG. Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J. Exp. Med. 181(6), 2109-2117 (1995
14. Mittendorf EA, Holmes JP, Ponniah S, Peoples GE. The E75 HER2/neu peptide vaccine. Cancer Immunol. Immunother. 57(10), 1511-1521 (2008
15. Soliman H. Developing an effective breast cancer vaccine. Cancer Control 17(3), 183-181 (2010
16. Chang F, Syrjanen S, Syrjanen K. Implications of the p53 tumor-suppressor gene in clinical oncology. J. Clin. Oncol. 13(4), 1009-1022 (1995
17. Runnebaum IB, Nagarajan M, Bowman M, Soto D, Sukumar S. Mutations in p53 as potential molecular markers for human breast cancer. Proc. Natl Acad. Sci. USA 88(23), 10657-10661 (1991 (Pubitemid 21915896)
18. Lutzker SG, Lattime EC. Use of dendritic cells to immunize against cancers overexpressing p53. Clin. Cancer Res. 7(1), 2-4 (2001 (Pubitemid 32110199)
19. Nikitina EY, Clark JI, Van Beynen J et al. Dendritic cells transduced with full-length wild-type p53 generate antitumor cytotoxic T lymphocytes from peripheral blood of cancer patients. Clin. Cancer Res. 7(1), 127-135 (2001 (Pubitemid 32110215)
20. Svane IM, Pedersen AE, Johnsen HE et al. Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a Phase I study. Cancer Immunol. Immunother. 53(7), 633-641 (2004 (Pubitemid 38858337)
21. Barfoed AM, Petersen TR, Kirkin AF et al. Cytotoxic T-lymphocyte clones, established by stimulation with the HLA-A2 binding p5365-73 wild type peptide loaded on dendritic cells in vitro, specifically recognize and lyse HLA-A2 tumour cells overexpressing the p53 protein. Scand. J. Immunol. 51(2), 128-133 (2000 (Pubitemid 30095758)
22. Ropke M, Hald J, Guldberg P 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. USA 93(25), 14704-14707 (1996 (Pubitemid 26419032)
23. Wurtzen PA, Claesson MH. A HLA-A2 restricted human CTL line recognizes a novel tumor cell expressed p53 epitope. Int. J. Cancer 99(4), 568-572 (2002 (Pubitemid 34461610)
24. Petersen TR, Buus S, Brunak S et al. Identification and design of p53-derived HLA-A2-binding peptides with increased CTL immunogenicity. Scand. J. Immunol. 53(4), 357-364 (2001 (Pubitemid 32275692)
25. Peoples GE, Holmes JP, Hueman MT et al. Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin. Cancer Res. 14(3), 797-803 (2008
26. Gillis S, Union NA, Baker PE, Smith KA. The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. J. Exp. Med. 149(6), 1460-1476 (1979 (Pubitemid 9209554)
27. Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity 33(2), 153-165 (2010
28. Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193(4257), 1007-1008 (1976
29. Goldstein AL, Badamchian M. Thymosins: chemistry and biological properties in health and disease. Expert Opin. Biol. Ther. 4(4), 559-573 (2004 (Pubitemid 38480555)
30. + stem cells into CD3+4+ cells in an in vitro thymic epithelia organ coculture model. Int. J. Immunopharmacol. 21(1), 15-26 (1999 (Pubitemid 29097685)
31. Romani L, Bistoni F, Gaziano R et al. Thymosin a 1 activates dendritic cells for antifungal Th1 resistance through Toll-like receptor signaling. Blood 103(11), 4232-4239 (2004 (Pubitemid 38685368)
32. Mittendorf EA, Gurney JM, Storrer CE et al. Vaccination with a HER2/neu peptide induces intra- and inter-antigenic epitope spreading in patients with early stage breast cancer. Surgery 139(3), 407-418 (2006
33. Mittendorf EA, Peoples GE. HER-2/neu peptide breast cancer vaccines: current status and future directions. Breast Diseases: A Year Book Quarterly 17(4), 318-320 (2007
34. Knutson KL, Disis ML. Augmenting T helper cell immunity in cancer. Curr. Drug Targets 5(4), 365-371 (2005). (Pubitemid 41722379)
35. Knutson KL, Schiffman K, Disis ML. Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients. J. Clin. Invest. 107(4), 477-484 (2001 (Pubitemid 32167994)
36. Karyampudi L, Formicola C, Erskine CL et al. A degenerate HLA-DR epitope pool of HER-2/neu reveals a novel in vivo immunodominant epitope, HER-2/neu88-102. Clin. Cancer Res. 16(3), 825-834 (2010
37. Karyampudi L, Krco CJ, Kalli KR et al. Identification of a broad coverage HLA-DR degenerate epitope pool derived from carcinoembryonic antigen. Cancer Immunol. Immunother. 59(1), 161-171 (2010
38. Mittendorf EA, Storrer CE, Foley RJ et al. Evaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast cancer vaccine trial. Cancer 106(11), 2309-2317 (2006 (Pubitemid 43787653)
39. Carmichael MG, Benavides LC, Holmes JP et al. Results of the first Phase 1 clinical trial of the HER-2/neu peptide (GP2) vaccine in disease-free breast cancer patients: United STATES Military Cancer Institute Clinical Trials Group Study I-04. Cancer 116(2), 292-301 (2010
40. + T cells in antitumor immunity: utility of an li-key HER2/neu hybrid peptide vaccine (AE37Expert Opin. Biol. Ther. 9(1), 71-78 (2009
41. Adams S, Humphreys RE. Invariant chain peptides enhancing or inhibiting the presentation of antigenic peptides by major histocompatibility complex class II molecules. Eur. J. Immunol. 25(6), 1693-1702 (1995
42. Xu M, Li J, Gulfo JV, Von Hofe E, Humphreys RE. MHC class II allosteric site drugs: new immunotherapeutics for malignant, infectious and autoimmune diseases. Scand. J. Immunol. 54(1-2), 39-44 (2001 (Pubitemid 32592326)
43. Gillogly ME, Kallinteris NL, Xu M et al. Ii-Key/HER-2/neu MHC class-II antigenic epitope vaccine peptide for breast cancer. Cancer Immunol. Immunother. 53(6), 490-496 (2004 (Pubitemid 38680255)
44. Humphreys RE, Adams S, Koldzic G et al. Increasing the potency of MHC class II-presented epitopes by linkage to Ii-Key peptide. Vaccine 18(24), 2693-2697 (2000 (Pubitemid 30211577)
45. + T cell-mediated antitumor responses by a helper HER-2/neu peptide linked to the Ii-Key moiety of the invariant chain. Int. J. Cancer 121(9), 2031-2041 (2007 (Pubitemid 47463167)
46. Holmes JP, Benavides LC, Gates JD et al. Results of the first Phase I clinical trial of the novel Ii-key hybrid preventive HER-2/neu peptide (AE37) vaccine. J. Clin. Oncol. 26(20), 3426-3433 (2008
47. Holmes JP, Clifton GT, Patil R et al. Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer 117(3), 463-471 (2010
48. Benavides LC, Gates JD, Carmichael MG et al. The impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin. Cancer Res. 15(8), 2895-2824 (2009
49. Knutson KL, Disis ML. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol. Immunother. 54(8), 721-728 (2005 (Pubitemid 40977140)
50. Disis ML, Wallace DR, Gooley TA et al. Concurrent trastuzumab and HER2/ neu-specific vaccination in patients with metastatic breast cancer. J. Clin. Oncol. 27(28), 4685-4692 (2009
51. + T cells stimulated by virus-induced type I interferon. Nat. Immunol. 4(10), 1009-1015 (2003 (Pubitemid 37265922)
52. + T cells: when, where, and how. Annu. Rev. Immunol. 24, 519-540 (2006
53. Drebin JA, Link VC, Stern DF, Weinberg RA, Greene MI. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell 41(3), 697-706 (1985
54. Hurwitz E, Klapper LN, Wilchek M, Yarden Y, Sela M. Inhibition of tumor growth by poly(ethylene glycol) derivatives of anti-ErbB2 antibodies. Cancer Immunol. Immunother. 49(4-5), 226-234 (2000 (Pubitemid 30484829)
55. Klapper LN, Waterman H, Sela M, Yarden Y. Tumor-inhibitory antibodies to HER-2/ ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res. 60(13), 3384-3388 (2000 (Pubitemid 30482151)
56. zum Buschenfelde CM, Hermann C, Schmidt B, Peschel C, Bernhard H. Antihuman epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab enhances cytolytic activity of class I-restricted HER2-specific T lymphocytes against HER2- overexpressing tumor cells. Cancer Res. 62(8), 2244-2247 (2002 (Pubitemid 34411698)
57. Mittendorf EA, Storrer CE, Shriver CD, Ponniah S, Peoples GE. Investigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancer. Ann. Surg. Oncol. 13(8), 1085-1098 2006 (Pubitemid 44337968)
58. Cox AL, Skipper J, Chen Y et al. Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 264(5159), 716-719 (1994 (Pubitemid 24185883)
59. Van Der Bruggen P, Zhang Y, Chaux P et al. Tumor-specific shared antigenic peptides recognized by human T cells. Immunol. Rev. 188, 51-64 (2002 (Pubitemid 35398865)
60. Huang AY, Bruce AT, Pardoll DM, Levitsky HI. In vivo cross-priming of MHC class I-restricted antigens requires the TAP transporter. Immunity 4(4), 349-355 (1996 (Pubitemid 26174050)
61. + T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J. Exp. Med. 200(3), 297-306 (2004 (Pubitemid 39031249)
62. Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392(6671), 86-89 (1998 (Pubitemid 28150594)
63. Huang AY, Golumbek P, Ahmadzadeh M et al. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264(5161), 961-965 (1994 (Pubitemid 24196166)
64. 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. 176(6), 1693-1702 (1992
65. 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 90(8), 3539-3543 (1993). (Pubitemid 23111402)
66. Jaffee EM, Hruban RH, Biedrzycki B et al. Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a Phase I trial of safety and immune activation. J. Clin. Oncol. 19(1), 145-156 (2001 (Pubitemid 32063491)
67. Laheru D, Lutz E, Burke J et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin. Cancer Res. 14(5), 1455-1463 (2008 (Pubitemid 351413929)
68. Nemunaitis J, Sterman D, Jablons D et al. Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J. Natl Cancer Inst. 96(4), 326-331 (2004 (Pubitemid 38256277)
69. Simons JW, Carducci MA, Mikhak B et al. Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naive prostate cancer. Clin. Cancer Res. 12(11 Pt 1), 3394-3401 (2006
70. Simons JW, Jaffee EM, Weber CE et al. Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer. Cancer Res. 57(8), 1537-1546 (1997 (Pubitemid 27175572)
71. 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. 61(9), 3689-3697 (2001 (Pubitemid 32694981)
72. + T-cell response to peptide vaccination: creation of a beneficial host microenvironment involving type I IFNs and myeloid cells. J. Immunother 30(1), 40-53 (2007 (Pubitemid 46052202)
73. Emens LA, Asquith JM, Leatherman JM et al. Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. J. Clin. Oncol. 27(35), 5911-5918 (2009
74. Davis-Sproul JM, Harris MP, Davidson NE et al. Cost-effective manufacture of an allogeneic GM-CSF-secreting breast tumor vaccine in an academic cGMP facility. Cytotherapy 7(1), 46-56 (2005 (Pubitemid 40542403)
75. Mescher MF. Surface contact requirements for activation of cytotoxic T lymphocytes. J. Immunol. 149(7), 2402-2405 (1992
76. Rogers J, Mescher MF. Augmentation of in vivo cytotoxic T lymphocyte activity and reduction of tumor growth by large multivalent immunogen. J. Immunol. 149(1), 269-276 (1992
77. Mitchell MS, Kan-Mitchell J, Morrow PR et al. Phase I trial of large multivalent immunogen derived from melanoma lysates in patients with disseminated melanoma. Clin. Cancer Res. 10(1 Pt 1), 76-83 (2004 (Pubitemid 38114164)
78. Hodge JW, McLaughlin JP, Kantor JA, Schlom J. Diversified prime and boost protocols using recombinant vaccinia virus and recombinant non-replicating avian pox virus to enhance T-cell immunity and antitumor responses. Vaccine 15(6-7), 759-768 (1997 (Pubitemid 27240492)
79. Marshall JL, Hoyer RJ, Toomey MA et al. Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J. Clin. Oncol. 18(23), 3964-3973 (2000
80. Tsang KY, Palena C, Gulley J, Arlen P, Schlom J. A human cytotoxic T-lymphocyte epitope and its agonist epitope from the nonvariable number of tandem repeat sequence of MUC-1. Clin. Cancer Res. 10(6), 2139-2149 (2004 (Pubitemid 38375576)
81. Tsang KY, Zaremba S, Nieroda CA et al. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J. Natl Cancer Inst. 87(13), 982-989 (1995
82. Garnett CT, Greiner JW, Tsang KY et al. TRICOM vector based cancer vaccines. Curr. Pharm. Des. 12(3), 351-361 (2006
83. Hodge JW, Chakraborty M, Kudo-Saito C, Garnett CT, Schlom J. Multiple costimulatory modalities enhance CTL avidity. J. Immunol. 174(10), 5994-6004 (2005 (Pubitemid 40663786)
84. Hodge JW, Sabzevari H, Yafal AG et al. A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res. 59(22), 5800-5807 (1999
85. Gulley JL, Arlen PM, Tsang KY et al. Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin. Cancer Res. 14(10), 3060-3069 (2008
86. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat. Med. 10(9), 9-915 (2004
87. Mittendorf EA, Peoples GE, Singletary SE. Breast cancer vaccines: promise for the future or pipe dream? Cancer 110(8), 1677-1686 (2007 (Pubitemid 47557292)
88. Mittendorf EA, Sharma P. Mechanisms of T-cell inhibition: implications for cancer immunotherapy. Expert Rev. Vaccines 9(1), 89-105 (2010
89. +CD25+ regulatory T cells by TGF-b induction of transcription factor FOXP3. J. Exp. Med. 198(12), 1875-1886 (2003 (Pubitemid 38032120)
90. Gabrilovich DI, Ishida T, Nadaf S, Ohm JE, Carbone DP. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin. Cancer Res. 5(10), 2963-2970 (1999 (Pubitemid 29493976)
91. Gorelik L, Flavell RA. Immune-mediated eradication of tumors through the blockade of transforming growth factor-b signaling in T cells. Nat. Med. 7(10), 1118-1122 (2001 (Pubitemid 33010019)
92. Kawamura K, Bahar R, Natsume W, Sakiyama S, Tagawa M. Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic antitumor immunity and impairs protective immunity induced against the tumors. Cancer Gene Ther. 9(1), 109-115 (2002 (Pubitemid 34052860)
93. McKallip R, Li R, Ladisch S. Tumor gangliosides inhibit the tumor-specific immune response. J. Immunol. 163(7), 3718-3726 (1999 (Pubitemid 29450894)
94. +25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 105(7), 2862-2868 (2005 (Pubitemid 40446280)
95. Ozao-Choy J, Ma G, Kao J et al. The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res. 69(6), 2514-2522 (2009
96. Hodi FS, O'Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363(8), 711-723 (2010
97. Vonderheide RH, LoRusso PM, Khalil M et al. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin. Cancer Res. 16(13), 3485-3494 (2010
98. +ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc. Natl Acad. Sci. USA 105(39), 14987-14992 (2008
99. Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol. Rev. 224, 141-165 (2008
100. Van der Burg SH. Therapeutic vaccines in cancer: moving from immunomonitoring to immunoguiding. Expert Rev. Vaccines 7(1), 1-5 (2008 (Pubitemid 351357961)
101. Welters MJ, Piersma SJ, van der Burg SH. T-regulatory cells in tumour-specific vaccination strategies. Expert Opin. Biol. Ther. 8(9), 1365-1379 (2008