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Published in:

01-09-2014

Immunotherapy for prostate cancer: recent developments and future challenges

Authors: Michael T. Schweizer, Charles G. Drake

Published in: Cancer and Metastasis Reviews | Issue 2-3/2014

Abstract

Since the approval of sipuleucel-T for men with metastatic castrate resistant prostate cancer in 2010, great strides in the development of anti-cancer immunotherapies have been made. Current drug development in this area has focused primarily on antigen-specific (i.e. cancer vaccines and antibody based therapies) or checkpoint inhibitor therapies, with the checkpoint inhibitors perhaps gaining the most attention as of late. Indeed, drugs blocking the inhibitory signal generated by the engagement of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) found on T-cells has emerged as potent means to combat the immunosuppressive milieu. The anti-CTLA-4 monoclonal antibody ipilimumab has already been approved in advanced melanoma and two phase III trials evaluating ipilimumab in men with metastatic castrate-resistant prostate cancer are underway. A phase III trial evaluating ProstVac-VF, a poxvirus-based therapeutic prostate cancer vaccine, is also underway. While there has been reason for encouragement over the past few years, many questions regarding the use of immunotherapies remain. Namely, it is unclear what stage of disease is most likely to benefit from these approaches, how best to incorporate said treatments with each other and into our current treatment regimens and which therapy is most appropriate for which disease. Herein we review some of the recent advances in immunotherapy as related to the treatment of prostate cancer and outline some of the challenges that lie ahead.

Siegel, R., Naishadham, D., & Jemal, A. (2013). Cancer statistics, 2013. CA Cancer J Clin, 63(1), 11–30. doi:10.3322/caac.21166.PubMedCrossRef

Huggins, C., & Hodges, C. V. (2002). Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol, 168(1), 9–12.PubMedCrossRef

Schweizer, M. T., & Antonarakis, E. S. (2012). Abiraterone and other novel androgen-directed strategies for the treatment of prostate cancer: a new era of hormonal therapies is born. Ther Adv Urol, 4(4), 167–178. doi:10.1177/1756287212452196.PubMedCentralPubMedCrossRef

Scher, H. I., Halabi, S., Tannock, I., Morris, M., Sternberg, C. N., Carducci, M. A., et al. (2008). Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol, 26(7), 1148–1159. doi:10.1200/jco.2007.12.4487.PubMedCentralPubMedCrossRef

Tannock, I. F., de Wit, R., Berry, W. R., Horti, J., Pluzanska, A., Chi, K. N., et al. (2004). Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med, 351(15), 1502–1512. doi:10.1056/NEJMoa040720.PubMedCrossRef

Petrylak, D. P., Tangen, C. M., Hussain, M. H., Lara, P. N., Jr., Jones, J. A., Taplin, M. E., et al. (2004). Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med, 351(15), 1513–1520. doi:10.1056/NEJMoa041318.PubMedCrossRef

Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., et al. (2010). Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med, 363(5), 411–422. doi:10.1056/NEJMoa1001294.PubMedCrossRef

de Bono, J. S., Oudard, S., Ozguroglu, M., Hansen, S., Machiels, J. P., Kocak, I., et al. (2010). Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet, 376(9747), 1147–1154. doi:10.1016/s0140-6736(10)61389-x.PubMedCrossRef

de Bono, J. S., Logothetis, C. J., Molina, A., Fizazi, K., North, S., Chu, L., et al. (2011). Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med, 364(21), 1995–2005. doi:10.1056/NEJMoa1014618.PubMedCentralPubMedCrossRef

10.

Ryan, C. J., Smith, M. R., de Bono, J. S., Molina, A., Logothetis, C. J., de Souza, P., et al. (2013). Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med, 368(2), 138–148. doi:10.1056/NEJMoa1209096.PubMedCentralPubMedCrossRef

11.

Scher, H. I., Fizazi, K., Saad, F., Taplin, M. E., Sternberg, C. N., Miller, K., et al. (2012). Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med, 367(13), 1187–1197. doi:10.1056/NEJMoa1207506.PubMedCrossRef

12.

Parker, C., Nilsson, S., Heinrich, D., Helle, S. I., O’Sullivan, J. M., Fossa, S. D., et al. (2013). Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med, 369(3), 213–223. doi:10.1056/NEJMoa1213755.PubMedCrossRef

13.

Aragon-Ching, J. B., Williams, K. M., & Gulley, J. L. (2007). Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer. Front Biosci, 12, 4957–4971.PubMedCrossRef

14.

Zitvogel, L., Apetoh, L., Ghiringhelli, F., & Kroemer, G. (2008). Immunological aspects of cancer chemotherapy. Nat Rev Immunol, 8(1), 59–73. doi:10.1038/nri2216.PubMedCrossRef

15.

Drake, C. G. (2011). Radiation-induced immune modulation. In T. L. L. DeWeese & M. Laiho (Eds.), Molecular Determinants of Radiation Response (pp. 251–263). New York: Springer.CrossRef

16.

Delves, P. J., & Roitt, I. M. (2000). The immune system. First of two parts. N Engl J Med, 343(1), 37–49. doi:10.1056/nejm200007063430107.PubMedCrossRef

17.

Delves, P. J., & Roitt, I. M. (2000). The immune system. Second of two parts. N Engl J Med, 343(2), 108–117. doi:10.1056/nejm200007133430207.PubMedCrossRef

18.

Simeone, E., & Ascierto, P. A. (2012). Immunomodulating antibodies in the treatment of metastatic melanoma: the experience with anti-CTLA-4, anti-CD137, and anti-PD1. J Immunotoxicol, 9(3), 241–247. doi:10.3109/1547691x.2012.678021.PubMedCrossRef

19.

Korman, A. J., Peggs, K. S., & Allison, J. P. (2006). Checkpoint blockade in cancer immunotherapy. Adv Immunol, 90, 297–339. doi:10.1016/s0065-2776(06)90008-x.PubMedCentralPubMedCrossRef

20.

Kwek, S. S., Dao, V., Roy, R., Hou, Y., Alajajian, D., Simko, J. P., et al. (2012). Diversity of antigen-specific responses induced in vivo with CTLA-4 blockade in prostate cancer patients. J Immunol, 189(7), 3759–3766. doi:10.4049/jimmunol.1201529.PubMedCentralPubMedCrossRef

21.

Kwek, S. S., Cha, E., & Fong, L. (2012). Unmasking the immune recognition of prostate cancer with CTLA4 blockade. Nat Rev Cancer, 12(4), 289–297. doi:10.1038/nrc3223.PubMedCentralPubMedCrossRef

22.

Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., et al. (2008). CTLA-4 control over Foxp3+ regulatory T cell function. Science, 322(5899), 271–275. doi:10.1126/science.1160062.PubMedCrossRef

23.

Quezada, S. A., Peggs, K. S., Curran, M. A., & Allison, J. P. (2006). CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Clin Invest, 116(7), 1935–1945. doi:10.1172/jci27745.PubMedCentralPubMedCrossRef

24.

Selby, M. J., Engelhardt, J. J., Quigley, M., Henning, K. A., Chen, T., Srinivasan, M., et al. (2013). Anti-CTLA-4 Antibodies of IgG2a Isotype Enhance Antitumor Activity through Reduction of Intratumoral Regulatory T Cells. Cancer Immunol Res, 1(1), 32–42. doi:10.1158/2326-6066/CIR-13-0013.PubMedCrossRef

25.

Simpson, T. R., Li, F., Montalvo-Ortiz, W., Sepulveda, M. A., Bergerhoff, K., Arce, F., et al. (2013). Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med, 210(9), 1695–1710. doi:10.1084/jem.20130579.PubMedCentralPubMedCrossRef

26.

Nemazee, D. (2006). Receptor editing in lymphocyte development and central tolerance. Nat Rev Immunol, 6(10), 728–740. doi:10.1038/nri1939.PubMedCrossRef

27.

Sheikh, N. A., Petrylak, D., Kantoff, P. W., Dela Rosa, C., Stewart, F. P., Kuan, L. Y., et al. (2013). Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer. Cancer Immunol Immunother, 62(1), 137–147. doi:10.1007/s00262-012-1317-2.PubMedCentralPubMedCrossRef

28.

Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011). Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science, 331(6024), 1565–1570. doi:10.1126/science.1203486.PubMedCrossRef

29.

Shankaran, V., Ikeda, H., Bruce, A. T., White, J. M., Swanson, P. E., Old, L. J., et al. (2001). IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature, 410(6832), 1107–1111. doi:10.1038/35074122.PubMedCrossRef

30.

Wang, X., Yu, J., Sreekumar, A., Varambally, S., Shen, R., Giacherio, D., et al. (2005). Autoantibody signatures in prostate cancer. N Engl J Med, 353(12), 1224–1235. doi:10.1056/NEJMoa051931.PubMedCrossRef

31.

Drake, C. G., Doody, A. D., Mihalyo, M. A., Huang, C. T., Kelleher, E., Ravi, S., et al. (2005). Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen. Cancer Cell, 7(3), 239–249. doi:10.1016/j.ccr.2005.01.027.PubMedCentralPubMedCrossRef

32.

Mercader, M., Bodner, B. K., Moser, M. T., Kwon, P. S., Park, E. S., Manecke, R. G., et al. (2001). T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc Natl Acad Sci U S A, 98(25), 14565–14570. doi:10.1073/pnas.251140998.PubMedCentralPubMedCrossRef

33.

Kovacs, W. J., & Olsen, N. J. (1987). Androgen receptors in human thymocytes. J Immunol, 139(2), 490–493.PubMed

34.

Viselli, S. M., Olsen, N. J., Shults, K., Steizer, G., & Kovacs, W. J. (1995). Immunochemical and flow cytometric analysis of androgen receptor expression in thymocytes. Mol Cell Endocrinol, 109(1), 19–26.PubMedCrossRef

35.

Cohen, J. H., Danel, L., Cordier, G., Saez, S., & Revillard, J. P. (1983). Sex steroid receptors in peripheral T cells: absence of androgen receptors and restriction of estrogen receptors to OKT8-positive cells. J Immunol, 131(6), 2767–2771.PubMed

36.

Benten, W. P., Lieberherr, M., Giese, G., Wrehlke, C., Stamm, O., Sekeris, C. E., et al. (1999). Functional testosterone receptors in plasma membranes of T cells. FASEB J, 13(1), 123–133.PubMed

37.

Pearce, P., Khalid, B. A., & Funder, J. W. (1981). Androgens and the thymus. Endocrinology, 109(4), 1073–1077.PubMedCrossRef

38.

Kumar, N., Shan, L. X., Hardy, M. P., Bardin, C. W., & Sundaram, K. (1995). Mechanism of androgen-induced thymolysis in rats. Endocrinology, 136(11), 4887–4893.PubMed

39.

Brelinska, R. (2003). Thymic epithelial cells in age-dependent involution. Microsc Res Tech, 62(6), 488–500. doi:10.1002/jemt.10410.PubMedCrossRef

40.

Sutherland, J. S., Goldberg, G. L., Hammett, M. V., Uldrich, A. P., Berzins, S. P., Heng, T. S., et al. (2005). Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol, 175(4), 2741–2753.PubMedCrossRef

41.

Olsen, N. J., Olson, G., Viselli, S. M., Gu, X., & Kovacs, W. J. (2001). Androgen receptors in thymic epithelium modulate thymus size and thymocyte development. Endocrinology, 142(3), 1278–1283.PubMed

42.

Dulos, G. J., & Bagchus, W. M. (2001). Androgens indirectly accelerate thymocyte apoptosis. Int Immunopharmacol, 1(2), 321–328.PubMedCrossRef

43.

Wilson, C. A., Mrose, S. A., & Thomas, D. W. (1995). Enhanced production of B lymphocytes after castration. Blood, 85(6), 1535–1539.PubMed

44.

Viselli, S. M., Reese, K. R., Fan, J., Kovacs, W. J., & Olsen, N. J. (1997). Androgens alter B cell development in normal male mice. Cell Immunol, 182(2), 99–104. doi:10.1006/cimm.1997.1227.PubMedCrossRef

45.

Roden, A. C., Moser, M. T., Tri, S. D., Mercader, M., Kuntz, S. M., Dong, H., et al. (2004). Augmentation of T cell levels and responses induced by androgen deprivation. J Immunol, 173(10), 6098–6108.PubMedCrossRef

46.

Marzo, A. L., Kinnear, B. F., Lake, R. A., Frelinger, J. J., Collins, E. J., Robinson, B. W., et al. (2000). Tumor-specific CD4+ T cells have a major “post-licensing” role in CTL mediated anti-tumor immunity. J Immunol, 165(11), 6047–6055.PubMedCrossRef

47.

Hung, K., Hayashi, R., Lafond-Walker, A., Lowenstein, C., Pardoll, D., & Levitsky, H. (1998). The central role of CD4(+) T cells in the antitumor immune response. J Exp Med, 188(12), 2357–2368.PubMedCentralPubMedCrossRef

48.

Dobrzanski, M. J. (2013). Expanding roles for CD4 T cells and their subpopulations in tumor immunity and therapy. Front Oncol, 3, 63. doi:10.3389/fonc.2013.00063.PubMedCentralPubMedCrossRef

49.

Gannon, P. O., Poisson, A. O., Delvoye, N., Lapointe, R., Mes-Masson, A. M., & Saad, F. (2009). Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients. J Immunol Methods, 348(1–2), 9–17. doi:10.1016/j.jim.2009.06.004.PubMedCrossRef

50.

Antonarakis, E. S., Kibel, A., Tyler, R. C., McCoy, C., Wang, Y., Sheikh, N. A., et al. (2013). Randomized phase II trial evaluating the optimal sequencing of sipuleucel-T and androgen-deprivation therapy (ADT) in patients (pts) with biochemically recurrent prostate cancer (BRPC) [abstract]. J Clin Oncol, 31, (suppl 6; abstr 34).

51.

Drake, C. G., Jaffee, E., & Pardoll, D. M. (2006). Mechanisms of immune evasion by tumors. Adv Immunol, 90, 51–81. doi:10.1016/s0065-2776(06)90002-9.PubMedCrossRef

52.

Hodi, F. S., O’Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., et al. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med, 363(8), 711–723. doi:10.1056/NEJMoa1003466.PubMedCentralPubMedCrossRef

53.

Robert, C., Thomas, L., Bondarenko, I., O’Day, S. M. D. J., Garbe, C., et al. (2011). Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med, 364(26), 2517–2526. doi:10.1056/NEJMoa1104621.PubMedCrossRef

54.

Kwon, E. D., Hurwitz, A. A., Foster, B. A., Madias, C., Feldhaus, A. L., Greenberg, N. M., et al. (1997). Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci U S A, 94(15), 8099–8103.PubMedCentralPubMedCrossRef

55.

Hurwitz, A. A., Foster, B. A., Kwon, E. D., Truong, T., Choi, E. M., Greenberg, N. M., et al. (2000). Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res, 60(9), 2444–2448.PubMed

56.

Demaria, S., Kawashima, N., Yang, A. M., Devitt, M. L., Babb, J. S., Allison, J. P., et al. (2005). Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res, 11(2 Pt 1), 728–734.PubMed

57.

Slovin, S. F., Higano, C. S., Hamid, O., Tejwani, S., Harzstark, A., Alumkal, J. J., et al. (2013). Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. doi:10.1093/annonc/mdt107.PubMedCentralPubMed

58.

Gerritsen, W. R., Kwon, E. D., Fizazi, K., Bossi, A., Van den Eertwegh, A., Logothetis, C., et al. (2013). CA184-043: A randomized, multicenter, double-blind phase 3 trial comparing overall survival (OS) in patients (pts) with post-docetaxel castration-resistant prostate cancer (CRPC) and bone metastases treated with ipilimumab (ipi) vs placebo (pbo), each following single-dose radiotherapy (RT) [abstract]. European Cancer Congress, abstr 2850.

59.

Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., et al. (2002). Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med, 8(8), 793–800. doi:10.1038/nm730.PubMed

60.

Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002). Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A, 99(19), 12293–12297. doi:10.1073/pnas.192461099.PubMedCentralPubMedCrossRef

61.

Taube, J. M., Anders, R. A., Young, G. D., Xu, H., Sharma, R., McMiller, T. L., et al. (2012). Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med, 4(127), 127ra–137ra. doi:10.1126/scitranslmed.3003689.CrossRef

62.

Hino, R., Kabashima, K., Kato, Y., Yagi, H., Nakamura, M., Honjo, T., et al. (2010). Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer, 116(7), 1757–1766. doi:10.1002/cncr.24899.PubMedCrossRef

63.

Barach, Y. S., Lee, J. S., & Zang, X. (2010). T cell coinhibition in prostate cancer: new immune evasion pathways and emerging therapeutics. Trends Mol Med. doi:10.1016/j.molmed.2010.09.006.PubMedCentralPubMed

64.

Sfanos, K. S., Bruno, T. C., Meeker, A. K., De Marzo, A. M., Isaacs, W. B., & Drake, C. G. (2009). Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. Prostate, 69(15), 1694–1703. doi:10.1002/pros.21020.PubMedCentralPubMedCrossRef

65.

Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., et al. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med, 366(26), 2443–2454. doi:10.1056/NEJMoa1200690.PubMedCentralPubMedCrossRef

66.

Brahmer, J. R., Tykodi, S. S., Chow, L. Q., Hwu, W. J., Topalian, S. L., Hwu, P., et al. (2012). Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med, 366(26), 2455–2465. doi:10.1056/NEJMoa1200694.PubMedCentralPubMedCrossRef

67.

Weiner, L. M., Surana, R., & Wang, S. (2010). Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol, 10(5), 317–327. doi:10.1038/nri2744.PubMedCentralPubMedCrossRef

68.

Topalian, S. L., Weiner, G. J., & Pardoll, D. M. (2011). Cancer immunotherapy comes of age. J Clin Oncol, 29(36), 4828–4836. doi:10.1200/jco.2011.38.0899.PubMedCentralPubMedCrossRef

69.

Mellman, I., Coukos, G., & Dranoff, G. (2011). Cancer immunotherapy comes of age. Nature, 480(7378), 480–489. doi:10.1038/nature10673.PubMedCentralPubMedCrossRef

70.

Drake, C. G. (2010). Prostate cancer as a model for tumour immunotherapy. Nat Rev Immunol, 10(8), 580–593. doi:10.1038/nri2817.PubMedCentralPubMedCrossRef

71.

Banchereau, J., & Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature, 392(6673), 245–252. doi:10.1038/32588.PubMedCrossRef

72.

Shurin, M. R. (1996). Dendritic cells presenting tumor antigen. Cancer Immunol Immunother, 43(3), 158–164.PubMedCrossRef

73.

Small, E. J., Fratesi, P., Reese, D. M., Strang, G., Laus, R., Peshwa, M. V., et al. (2000). Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol, 18(23), 3894–3903.PubMed

74.

Madan, R. A., Gulley, J. L., & Kantoff, P. W. (2013). Demystifying immunotherapy in prostate cancer: understanding current and future treatment strategies. Cancer J, 19(1), 50–58. doi:10.1097/PPO.0b013e31828160a9.PubMedCentralPubMedCrossRef

75.

Huber, M. L., Haynes, L., Parker, C., & Iversen, P. (2012). Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst, 104(4), 273–279. doi:10.1093/jnci/djr514.PubMedCentralPubMedCrossRef

76.

Mackall, C. L., Hakim, F. T., & Gress, R. E. (1997). Restoration of T-cell homeostasis after T-cell depletion. Semin Immunol, 9(6), 339–346. doi:10.1006/smim.1997.0091.PubMedCrossRef

77.

Drake, C. G. (2012). Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst, 104(18), 1422. doi:10.1093/jnci/djs340. author reply 1422-1423.PubMedCrossRef

78.

Gulley, J. L., Leitman, S. F., Dahut, W., & Schlom, J. (2012). Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst, 104(14), 1106. doi:10.1093/jnci/djs280. author reply 1109-1112.PubMedCrossRef

79.

Simons, J. W., Carducci, M. A., Mikhak, B., Lim, M., Biedrzycki, B., Borellini, F., et al. (2006). Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naive prostate cancer. Clin Cancer Res, 12(11 Pt 1), 3394–3401. doi:10.1158/1078-0432.ccr-06-0145.PubMedCrossRef

80.

Dranoff, G., Jaffee, E., Lazenby, A., Golumbek, P., Levitsky, H., Brose, K., et al. (1993). 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 U S A, 90(8), 3539–3543.PubMedCentralPubMedCrossRef

81.

Small, E. J., Tchekmedyian, N. S., Rini, B. I., Fong, L., Lowy, I., & Allison, J. P. (2007). A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin Cancer Res, 13(6), 1810–1815. doi:10.1158/1078-0432.ccr-06-2318.PubMedCrossRef

82.

Small, E. J., Demkow, T., Gerritson, W. R., Rolland, F., Hoskin, P., Smith, D. C., et al. (2009). A phase III trial of GVAX immunotherapy for prostate cancer in combination with docetaxel vs. docetaxel plus prednisone in symptomatic, castration-resistant prostate cancer (CRPC) [Abstract]. American Society of Clinical Oncology Genitourinary Cancers Symposium, (Abstr 9).

83.

Wada, S., Yoshimura, K., Hipkiss, E. L., Harris, T. J., Yen, H. R., Goldberg, M. V., et al. (2009). Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res, 69(10), 4309–4318. doi:10.1158/0008-5472.can-08-4102.PubMedCentralPubMedCrossRef

84.

Arlen, P. M., Gulley, J. L., Madan, R. A., Hodge, J. W., & Schlom, J. (2007). Preclinical and clinical studies of recombinant poxvirus vaccines for carcinoma therapy. Crit Rev Immunol, 27(5), 451–462.PubMedCrossRef

85.

Harrington, L. E., Most Rv, R., Whitton, J. L., & Ahmed, R. (2002). Recombinant vaccinia virus-induced T-cell immunity: quantitation of the response to the virus vector and the foreign epitope. J Virol, 76(7), 3329–3337.PubMedCentralPubMedCrossRef

86.

Madan, R. A., Arlen, P. M., Mohebtash, M., Hodge, J. W., & Gulley, J. L. (2009). Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs, 18(7), 1001–1011. doi:10.1517/13543780902997928.PubMedCentralPubMedCrossRef

87.

Kaufman, H. L., Wang, W., Manola, J., DiPaola, R. S., Ko, Y. J., Sweeney, C., et al. (2004). Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol, 22(11), 2122–2132. doi:10.1200/jco.2004.08.083.PubMedCrossRef

88.

Kaufman, H. L., Wang, W., Manola, J., DiPaola, R. S., Ko, Y. J., Sweeney, C. J., et al. (2005). Phase II prime/boost vaccination using poxviruses expressing PSA in hormone-dependent prostate cancer: follow-up clinical results from ECOG 7897 [abstract]. J Clin Oncol, 23(16S), 4501.

89.

Alam, S., & McNeel, D. G. (2010). DNA vaccines for the treatment of prostate cancer. Expert Rev Vaccines, 9(7), 731–745. doi:10.1586/erv.10.64.PubMedCrossRef

90.

Becker, J. T., Olson, B. M., Johnson, L. E., Davies, J. G., Dunphy, E. J., & McNeel, D. G. (2010). DNA vaccine encoding prostatic acid phosphatase (PAP) elicits long-term T-cell responses in patients with recurrent prostate cancer. J Immunother, 33(6), 639–647. doi:10.1097/CJI.0b013e3181dda23e.PubMedCentralPubMedCrossRef

91.

McNeel, D. G., Dunphy, E. J., Davies, J. G., Frye, T. P., Johnson, L. E., Staab, M. J., et al. (2009). Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer. J Clin Oncol, 27(25), 4047–4054. doi:10.1200/jco.2008.19.9968.PubMedCentralPubMedCrossRef

92.

Li, S., Schmitz, K. R., Jeffrey, P. D., Wiltzius, J. J., Kussie, P., & Ferguson, K. M. (2005). Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell, 7(4), 301–311. doi:10.1016/j.ccr.2005.03.003.PubMedCrossRef

93.

Clynes, R. A., Towers, T. L., Presta, L. G., & Ravetch, J. V. (2000). Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med, 6(4), 443–446. doi:10.1038/74704.PubMedCrossRef

94.

Verma, S., Miles, D., Gianni, L., Krop, I. E., Welslau, M., Baselga, J., et al. (2012). Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med, 367(19), 1783–1791. doi:10.1056/NEJMoa1209124.PubMedCrossRef

95.

Akhtar, N. H., Pail, O., Saran, A., Tyrell, L., & Tagawa, S. T. (2012). Prostate-specific membrane antigen-based therapeutics. Adv Urol, 2012, 973820. doi:10.1155/2012/973820.PubMedCentralPubMedCrossRef

96.

Morris, M. J., Divgi, C. R., Pandit-Taskar, N., Batraki, M., Warren, N., Nacca, A., et al. (2005). Pilot trial of unlabeled and indium-111-labeled anti-prostate-specific membrane antigen antibody J591 for castrate metastatic prostate cancer. Clin Cancer Res, 11(20), 7454–7461. doi:10.1158/1078-0432.ccr-05-0826.PubMedCrossRef

97.

Bander, N. H., Milowsky, M. I., Nanus, D. M., Kostakoglu, L., Vallabhajosula, S., & Goldsmith, S. J. (2005). Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. J Clin Oncol, 23(21), 4591–4601. doi:10.1200/jco.2005.05.160.PubMedCrossRef

98.

Hurwitz, A. A., Yu, T. F., Leach, D. R., & Allison, J. P. (1998). CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc Natl Acad Sci U S A, 95(17), 10067–10071.PubMedCentralPubMedCrossRef

99.

van Elsas, A., Hurwitz, A. A., & Allison, J. P. (1999). Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med, 190(3), 355–366.PubMedCentralPubMedCrossRef

100.

Woo, S. R., Turnis, M. E., Goldberg, M. V., Bankoti, J., Selby, M., Nirschl, C. J., et al. (2012). Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res, 72(4), 917–927. doi:10.1158/0008-5472.can-11-1620.PubMedCentralPubMedCrossRef

101.

Fong, L., Kwek, S. S., O’Brien, S., Kavanagh, B., McNeel, D. G., Weinberg, V., et al. (2009). Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF. Cancer Res, 69(2), 609–615. doi:10.1158/0008-5472.can-08-3529.PubMedCrossRef

102.

van den Eertwegh, A. J., Versluis, J., van den Berg, H. P., Santegoets, S. J., van Moorselaar, R. J., van der Sluis, T. M., et al. (2012). Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol, 13(5), 509–517. doi:10.1016/s1470-2045(12)70007-4.PubMedCrossRef

103.

Harzstark, A. L., Fong, L., Weinberg, V. K., Ryan, C. J., Lin, A. M., Sun, J., et al. (2010). Final results of a phase I study of CTLA-4 blockade in combination with GM-CSF for metastatic castration resistant prostate cancer (mCRPC) [Abstract]. J Clin Oncol 28:15s, 2010 (suppl; abstr 4689)

104.

Gerritsen, W. R., van den Eertwegh, A. J., de Gruijl, T. D., Giaccone, G., Scheper, R. J., Sacks, N., et al. (2007). Biochemical and immunologic correlates of clinical response in a combination trial of the GM-CSF-gene transduced allogeneic prostate cancer immunotherapy and ipilimumab in patients with metastatic hormone-refractory prostate cancer (mHRPC) [Abstract]. J Clin Oncol 25:18s (suppl; abstr 5120).

105.

Zitvogel, L., Apetoh, L., Ghiringhelli, F., Andre, F., Tesniere, A., & Kroemer, G. (2008). The anticancer immune response: indispensable for therapeutic success? J Clin Invest, 118(6), 1991–2001. doi:10.1172/jci35180.PubMedCentralPubMedCrossRef

106.

Ma, Y., Kepp, O., Ghiringhelli, F., Apetoh, L., Aymeric, L., Locher, C., et al. (2010). Chemotherapy and radiotherapy: cryptic anticancer vaccines. Semin Immunol, 22(3), 113–124. doi:10.1016/j.smim.2010.03.001.PubMedCrossRef

107.

Tanaka, H., Matsushima, H., Mizumoto, N., & Takashima, A. (2009). Classification of chemotherapeutic agents based on their differential in vitro effects on dendritic cells. Cancer Res, 69(17), 6978–6986. doi:10.1158/0008-5472.can-09-1101.PubMedCentralPubMedCrossRef

108.

Formenti, S. C., & Demaria, S. (2013). Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst, 105(4), 256–265. doi:10.1093/jnci/djs629.PubMedCentralPubMedCrossRef

109.

den Boer, A. T., van Mierlo, G. J., Fransen, M. F., Melief, C. J., Offringa, R., & Toes, R. E. (2004). The tumoricidal activity of memory CD8+ T cells is hampered by persistent systemic antigen, but full functional capacity is regained in an antigen-free environment. J Immunol, 172(10), 6074–6079.CrossRef

110.

Finn, O. J. (2003). Cancer vaccines: between the idea and the reality. Nat Rev Immunol, 3(8), 630–641. doi:10.1038/nri1150.PubMedCrossRef

111.

Gulley, J. L., Arlen, P. M., Madan, R. A., Tsang, K. Y., Pazdur, M. P., Skarupa, L., et al. (2010). Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother, 59(5), 663–674. doi:10.1007/s00262-009-0782-8.PubMedCentralPubMedCrossRef

112.

Motoyoshi, Y., Kaminoda, K., Saitoh, O., Hamasaki, K., Nakao, K., Ishii, N., et al. (2006). Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide. Oncol Rep, 16(1), 141–146.PubMed

113.

Mole, R. H. (1953). Whole body irradiation; radiobiology or medicine? Br J Radiol, 26(305), 234–241.PubMedCrossRef

114.

Demaria, S., Ng, B., Devitt, M. L., Babb, J. S., Kawashima, N., Liebes, L., et al. (2004). Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys, 58(3), 862–870. doi:10.1016/j.ijrobp.2003.09.012.PubMedCrossRef

115.

Chi, K. H., Liu, S. J., Li, C. P., Kuo, H. P., Wang, Y. S., Chao, Y., et al. (2005). Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother, 28(2), 129–135.PubMedCrossRef

116.

Finkelstein, S. E., Iclozan, C., Bui, M. M., Cotter, M. J., Ramakrishnan, R., Ahmed, J., et al. (2012). Combination of external beam radiotherapy (EBRT) with intratumoral injection of dendritic cells as neo-adjuvant treatment of high-risk soft tissue sarcoma patients. Int J Radiat Oncol Biol Phys, 82(2), 924–932. doi:10.1016/j.ijrobp.2010.12.068.PubMedCrossRef

117.

Brody, J. D., Ai, W. Z., Czerwinski, D. K., Torchia, J. A., Levy, M., Advani, R. H., et al. (2010). In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study. J Clin Oncol, 28(28), 4324–4332. doi:10.1200/jco.2010.28.9793.PubMedCentralPubMedCrossRef

118.

Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., et al. (2013). Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. doi:10.1056/NEJMoa1302369.

119.

Hamid, O., Robert, C., Daud, A., Hodi, F. S., Hwu, W. J., Kefford, R., et al. (2013). Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. doi:10.1056/NEJMoa1305133.PubMed

120.

Wolchok, J. D., Hoos, A., O’Day, S., Weber, J. S., Hamid, O., Lebbe, C., et al. (2009). Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res, 15(23), 7412–7420. doi:10.1158/1078-0432.ccr-09-1624.PubMedCrossRef

Title: Immunotherapy for prostate cancer: recent developments and future challenges
Authors: Michael T. Schweizer
Charles G. Drake
Publication date: 01-09-2014
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 2-3/2014
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-013-9479-8

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