A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: Immune correlates

Cancer Immunology, Immunotherapy

Volumn 63, Issue 4, 2014, Pages 407-418

  Jochems, Caroline ^a   Tucker, Jo A ^a   Tsang, Kwong Yok ^a   Madan, Ravi A ^a   Dahut, William L ^a   Liewehr, David J ^a   Steinberg, Seth M ^a   Gulley, James L ^a   Schlom, Jeffrey ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Immunotherapy; Ipilimumab; NK cells; PROSTVAC; T cells; Vaccine

Indexed keywords

APC PROTEIN; CD11B ANTIGEN; CD16 ANTIGEN; CD4 ANTIGEN; CD8 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; HEMOGLOBIN; INTERLEUKIN 17; IPILIMUMAB; L SELECTIN; PROGRAMMED DEATH 1 RECEPTOR; PROSTATE SPECIFIC ANTIGEN; RILIMOGENE GALVACIREPVEC;

ARTICLE; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CASTRATION RESISTANT PROSTATE CANCER; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; FLOW CYTOMETRY; FOLLOW UP; GLEASON SCORE; HELPER CELL; HUMAN; HUMAN CELL; HUMAN TISSUE; LYMPHOCYTE COUNT; MAINTENANCE DRUG DOSE; MALE; METASTASIS; NATURAL KILLER CELL; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 1 CLINICAL TRIAL (TOPIC); PHENOTYPE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SURVIVAL TIME; T LYMPHOCYTE; TH17 CELL;

ADENOCARCINOMA; ANTIBODIES, MONOCLONAL; ANTIGENS, DIFFERENTIATION; CANCER VACCINES; COMBINED MODALITY THERAPY; FLOW CYTOMETRY; HUMANS; IMMUNOPHENOTYPING; KAPLAN-MEIER ESTIMATE; KILLER CELLS, NATURAL; LYMPHOCYTE COUNT; MALE; MEMBRANE PROTEINS; PROSTATE-SPECIFIC ANTIGEN; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY; TH17 CELLS; VACCINES, SYNTHETIC;

EID: 84896489380     PISSN: 03407004     EISSN: 14320851     Source Type: Journal    
DOI: 10.1007/s00262-014-1524-0     Document Type: Article

References (53)

1. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411-422. doi:10.1056/NEJMoa1001294
2. Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, Manson K, Panicali DL, Laus R, Schlom J, Dahut WL, Arlen PM, Gulley JL, Godfrey WR (2010) Overall survival analysis of a phase II randomized controlled trial of a poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol 28:1099-1105. doi:10.1200/JCO.2009.25.0597
3. Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, Jones JL, Poole DJ, Higgins JP, Hodge JW, Cereda V, Vergati M, Steinberg SM, Halabi S, Jones E, Chen C, Parnes H, Wright JJ, Dahut WL, Schlom J (2010) Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother 59:663-674. doi:10.1007/s00262-009-0782-8
4. A Randomized, Double-blind, Phase 3 Efficacy Trial of PROS-TVAC- V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer (Prospect) http://clinicaltrials.gov/ct2/ show/NCT01322490
5. Hodge JW, Sabzevari H, Yafal AG, Gritz L, Lorenz MG, Schlom J (1999) A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res 59:5800-5807
6. Halabi S, Small EJ, Kantoff PW, Kattan MW, Kaplan EB, Dawson NA, Levine EG, Blumenstein BA, Vogelzang NJ (2003) Prognostic model for predicting survival in men with hormonerefractory metastatic prostate cancer. J Clin Oncol 21:1232-1237. doi:10.1200/JCO.2003.06.100 (Pubitemid 46606398)
7. Vergati M, Cereda V, Madan RA, Gulley JL, Huen NY, Rogers CJ, Hance KW, Arlen PM, Schlom J, Tsang KY (2011) Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination. Cancer Immunol Immunother 60:197-206. doi:10.1007/s00262-010-0927-9
8. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711-723. doi:10.1056/NEJMoa1003466
9. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517-2526. doi:10.1056/ NEJMoa1104621
10. Small EJ, Tchekmedyian NS, Rini BI, Fong L, Lowy I, Allison JP (2007) A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin Cancer Res 13:1810-1815. doi:10.1158/1078-0432.CCR-06-2318 (Pubitemid 46952950)
11. Slovin SF, Higano CS, Hamid O, Tejwani S, Harzstark A, Alumkal JJ, Scher HI, Chin K, Gagnier P, McHenry MB, Beer TM (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 24:1813-1821. doi:10.1093/annonc/mdt107
12. Madan RA, Mohebtash M, Arlen PM, Vergati M, Rauckhorst M, Steinberg SM, Tsang KY, Poole DJ, Parnes HL, Wright JJ, Dahut WL, Schlom J, Gulley JL (2012) Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol 13:501-508. doi:10.1016/S1470-2045(12)70006-2
13. Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745-763. doi:10.1146/annu rev.immunol.22.012703.104702
14. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, Nomura T, Sakaguchi S (2008) CTLA-4 control over Foxp3 + regulatory T cell function. Science 322:271-275. doi:10.1126/science.1160062
15. Huen NY, Pang AL, Tucker JA, Lee TL, Vergati M, Jochems C, Intrivici C, Cereda V, Chan WY, Rennert OM, Madan RA, Gulley JL, Schlom J, Tsang KY (2013) Up-regulation of proliferative and migratory genes in regulatory T cells from patients with metastatic castration-resistant prostate cancer. Int J Cancer. doi:10.1002/ijc.28026
16. Ndhlovu LC, Lopez-Verges S, Barbour JD, Jones RB, Jha AR, Long BR, Schoeffler EC, Fujita T, Nixon DF, Lanier LL (2012) Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood 119:3734-3743. doi:10.1182/blood-2011-11-392951
17. Beziat V, Duffy D, Quoc SN, Le Garff-Tavernier M, Decocq J, Combadiere B, Debre P, Vieillard V (2011) CD56brightCD16 + NK cells: a functional intermediate stage of NK cell differentiation. J Immunol 186:6753-6761. doi:10.4049/jimmunol.1100330
18. Vuk-Pavlovic S, Bulur PA, Lin Y, Qin R, Szumlanski CL, Zhao X, Dietz AB (2010) Immunosuppressive CD14 + HLA-DRlow/monocytes in prostate cancer. Prostate 70:443-455. doi:10.1002/pros.21078
19. Greten TF, Manns MP, Korangy F (2011) Myeloid derived suppressor cells in human diseases. Int Immunopharmacol 11:802-807. doi:10.1016/j.intimp.2011.01. 003
20. Vaccine and Antibody Treatment of Prostate Cancer. http://clinicaltrials. gov/show/NCT00113984
21. Teeter AE, Presti JC Jr, Aronson WJ, Terris MK, Kane CJ, Amling CL, Freedland SJ (2011) Does PSADT after radical prostatectomy correlate with overall survival? - a report from the SEARCH database group. Urology 77:149-153. doi:10.1016/j. urology.2010.04.071
22. Vesalainen S, Lipponen P, Talja M, Syrjanen K (1994) Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 30A:1797-1803 (Pubitemid 24377155)
23. Karja V, Aaltomaa S, Lipponen P, Isotalo T, Talja M, Mokka R (2005) Tumour-infiltrating lymphocytes: a prognostic factor of PSA-free survival in patients with local prostate carcinoma treated by radical prostatectomy. Anticancer Res 25:4435-4438 (Pubitemid 41729492)
24. Mercader M, Bodner BK, Moser MT, Kwon PS, Park ES, Manecke RG, Ellis TM, Wojcik EM, Yang D, Flanigan RC, Waters WB, Kast WM, Kwon ED (2001) T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc Natl Acad Sci USA 98:14565-14570. doi:10.1073/pnas. 251140998 (Pubitemid 33121432)
25. Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG (2008) Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14:3254-3261. doi:10.1158/1078-0432.CCR-07-5164
26. Yang S, Hodge JW, Grosenbach DW, Schlom J (2005) Vaccines with enhanced costimulation maintain high avidity memory CTL. J Immunol 175:3715-3723 (Pubitemid 41292031)
27. Hodge JW, Chakraborty M, Kudo-Saito C, Garnett CT, Schlom J (2005) Multiple costimulatory modalities enhance CTL avidity. J Immunol 174:5994-6004 (Pubitemid 40663786)
28. Chakraborty M, Schlom J, Hodge JW (2007) The combined activation of positive costimulatory signals with modulation of a negative costimulatory signal for the enhancement of vaccine-mediated T-cell responses. Cancer Immunol Immunother 56:1471-1484. doi:10.1007/s00262-007-0291-6 (Pubitemid 47024711)
29. van den Eertwegh AJ, Versluis J, van den Berg HP, Santegoets SJ, van Moorselaar RJ, van der Sluis TM, Gall HE, Harding TC, Jooss K, Lowy I, Pinedo HM, Scheper RJ, Stam AG, von Blomberg BM, de Gruijl TD, Hege K, Sacks N, Gerritsen WR (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 13:509-517. doi:10.1016/S1470- 2045(12)70007-4
30. Gerritsen WR (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). The European Cancer Congress, Sept. 27-Oct. 1, 2013; abstr 2850
31. Ku GY, Yuan J, Page DB, Schroeder SE, Panageas KS, Carvajal RD, Chapman PB, Schwartz GK, Allison JP, Wolchok JD (2010) Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Cancer 116:1767-1775. doi:10.1002/cncr.24951
32. Berman D, Wolchok J, Weber J, Hamid O, O'Day S, Chasalow S (2009) Association of peripheral blood absolute lymphocyte count (ALC) and clinical activity in patients (pts) with advanced melanoma treated with ipilimumab. J Clin Oncol 27(Suppl; abstr 3020)
33. Liakou CI, Kamat A, Tang DN, Chen H, Sun J, Troncoso P, Logothetis C, Sharma P (2008) CTLA-4 blockade increases IFNgamma-producing CD4 + ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci USA 105:14987-14992. doi:10.1073/pnas.0806075105
34. Chen H, Liakou CI, Kamat A, Pettaway C, Ward JF, Tang DN, Sun J, Jungbluth AA, Troncoso P, Logothetis C, Sharma P (2009) Anti-CTLA-4 therapy results in higher CD4 + ICOShi T cell frequency and IFN-gamma levels in both nonmalignant and malignant prostate tissues. Proc Natl Acad Sci USA 106:2729-2734. doi:10.1073/pnas.0813175106
35. Mahajan S, Cervera A, MacLeod M, Fillatreau S, Perona-Wright G, Meek S, Smith A, MacDonald A, Gray D (2007) The role of ICOS in the development of CD4 T cell help and the reactivation of memory T cells. Eur J Immunol 37:1796-1808. doi:10.1002/ eji.200636661
36. Moore TV, Clay BS, Ferreira CM, Williams JW, Rogozinska M, Cannon JL, Shilling RA, Marzo AL, Sperling AI (2011) Protective effector memory CD4 T cells depend on ICOS for survival. PLoS ONE 6:e16529. doi:10.1371/journal.pone. 0016529
37. Fu T, He Q, Sharma P (2011) The ICOS/ICOSL pathway is required for optimal antitumor responses mediated by anti-CTLA-4 therapy. Cancer Res 71:5445-5454. doi:10.1158/0008-5472.CAN-11-1138
38. Carthon BC, Wolchok JD, Yuan J, Kamat A, Ng Tang DS, Sun J, Ku G, Troncoso P, Logothetis CJ, Allison JP, Sharma P (2010) Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res 16:2861-2871. doi:10.1158/1078-0432.CCR-10-0569
39. Corthay A, Skovseth DK, Lundin KU, Rosjo E, Omholt H, Hofgaard PO, Haraldsen G, Bogen B (2005) Primary antitumor immune response mediated by CD4 + T cells. Immunity 22:371-383. doi:10.1016/j.immuni.2005.02.003 (Pubitemid 40387478)
40. Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, Roddie C, Henry JY, Yagita H, Wolchok JD, Peggs KS, Ravetch JV, Allison JP, Quezada SA (2013) Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. doi:10.10 84/jem.20130579
41. Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP (2009) Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 206:1717-1725. doi:10.1084/jem.20082492
42. Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z, Finger LR (1997) Activation-induced expression of human programmed death-1 gene in T-lymphocytes. Exp Cell Res 232:25-28. doi:10.1006/excr 1997.3493
43. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443-2454. doi:10.1056/NEJ Moa1200690
44. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455-2465. doi:10.1056/NEJMoa1200694
45. Jin HT, Anderson AC, Tan WG, West EE, Ha SJ, Araki K, Freeman GJ, Kuchroo VK, Ahmed R (2010) Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci USA 107:14733-14738. doi:10.1073/pnas.1009731107
46. Qiu Y, Chen J, Liao H, Zhang Y, Wang H, Li S, Luo Y, Fang D, Li G, Zhou B, Shen L, Chen CY, Huang D, Cai J, Cao K, Jiang L, Zeng G, Chen ZW (2012) Tim-3-expressing CD4 + and CD8 + T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions. PLoS Pathog 8:e1002984. doi:10.1371/journal.ppat.1002984
47. Gleason MK, Lenvik TR, McCullar V, Felices M, O'Brien MS, Cooley SA, Verneris MR, Cichocki F, Holman CJ, Panoskaltsis- Mortari A, Niki T, Hirashima M, Blazar BR, Miller JS (2012) Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9. Blood 119:3064-3072. doi:10.1182/blood-2011-06-360321
48. Kudo-Saito C, Garnett CT, Wansley EK, Schlom J, Hodge JW (2007) Intratumoral delivery of vector mediated IL-2 in combination with vaccine results in enhanced T cell avidity and antitumor activity. Cancer Immunol Immunother 56:1897-1910. doi:10.1007/s00262-007-0332-1 (Pubitemid 47512611)
49. Kudo-Saito C, Schlom J, Camphausen K, Coleman CN, Hodge JW (2005) The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors. Clin Cancer Res 11:4533-4544. doi:10.1158/1078-0432.CCR-04-2237 (Pubitemid 40825644)
50. Disis ML (2009) Enhancing cancer vaccine efficacy via modulation of the tumor microenvironment. Clin Cancer Res 15:6476-6478. doi:10.1158/1078-0432.CCR- 09-2256
51. Disis ML (2011) Immunologic biomarkers as correlates of clinical response to cancer immunotherapy. Cancer Immunol Immunother 60:433-442. doi:10.1007/s00262-010-0960-8
52. Hardwick N, Chain B (2011) Epitope spreading contributes to effective immunotherapy in metastatic melanoma patients. Immunotherapy 3:731-733. doi:10.2217/imt.11.62
53. Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich PY, Mendrzyk R, Hilf N, Schoor O, Fritsche J, Mahr A, Maurer D, Vass V, Trautwein C, Lewandrowski P, Flohr C, Pohla H, Stanczak JJ, Bronte V, Mandruzzato S, Biedermann T, Pawelec G, Derhovanessian E, Yamagishi H, Miki T, Hongo F, Takaha N, Hirakawa K, Tanaka H, Stevanovic S, Frisch J, Mayer-Mokler A, Kirner A, Rammensee HG, Reinhardt C, Singh-Jasuja H (2012) Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med 18:1254-1261. doi:10.1038/nm.2883