Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

We recently reported the clinical results of a Phase I trial combining ipilimumab with a vaccine containing transgenes for prostate-specific antigen (PSA) and for a triad of costimulatory molecules (PROSTVAC) in patients with metastatic castration-resistant prostate cancer. Thirty patients were treated with escalating ipilimumab and a fixed dose of vaccine. Of 24 chemotherapy-naïve patients, 58 % had a PSA decline. Combination therapy did not exacerbate the immune-related adverse events associated with ipilimumab. Here, we present updated survival data and an evaluation of 36 immune cell subsets pre- and post-therapy. Peripheral blood mononuclear cells were collected before therapy, at 13 days and at 70 days post-initiation of therapy, and phenotyped by flow cytometry for the subsets of T cells, regulatory T cells, natural killer cells, and myeloid-derived suppressor cells. Associations between overall survival (OS) and immune cell subsets prior to treatment, and the change in a given immune cell subset 70 days post-initiation of therapy, were evaluated. The median OS was 2.63 years (1.77–3.45). There were trends toward associations for longer OS and certain immune cell subsets before immunotherapy: lower PD-1+Tim-3NEGCD4EM (P = 0.005, adjusted P = 0.010), higher PD-1NEGTim-3+CD8 (P = 0.002, adjusted P = 0.004), and a higher number of CTLA-4NEG Tregs (P = 0.005, adjusted P = 0.010). We also found that an increase in Tim-3+ natural killer cells post- versus pre-vaccination associated with longer OS (P = 0.0074, adjusted P = 0.015). These results should be considered as hypothesis generating and should be further evaluated in larger immunotherapy trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ALC:

Absolute lymphocyte count

CTLA-4:

Cytotoxic T-lymphocyte-associated antigen-4

DT:

Doubling time

EM:

Effector memory

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

ICOS:

Inducible costimulator

IFN:

Interferon

IL:

Interleukin

mCRPC:

Metastatic castration-resistant prostate cancer

MDSC:

Myeloid-derived suppressor cell

NK:

Natural killer

OS:

Overall survival

PAP:

Prostatic acid phosphatase

PBMC:

Peripheral blood mononuclear cell

PD-1:

Programmed death 1 receptor

PSA:

Prostate-specific antigen

PSMA:

Prostate-specific membrane antigen

TIM-3:

T-cell immunoglobulin and mucin domain-containing molecule-3

Tregs:

Regulatory T cells

TRICOM:

Triad of costimulatory molecules (ICAM-1, B7.1, and LFA-3)

References

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-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

    CAS  PubMed  Google Scholar 

  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 hormone-refractory metastatic prostate cancer. J Clin Oncol 21:1232–1237. doi:10.1200/JCO.2003.06.100

    Article  PubMed  Google Scholar 

  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

    Article  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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/annurev.immunol.22.012703.104702

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Yang S, Hodge JW, Grosenbach DW, Schlom J (2005) Vaccines with enhanced costimulation maintain high avidity memory CTL. J Immunol 175:3715–3723

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Hodge JW, Chakraborty M, Kudo-Saito C, Garnett CT, Schlom J (2005) Multiple costimulatory modalities enhance CTL avidity. J Immunol 174:5994–6004

    CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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:10.1084/jem.20130579

    PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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/NEJMoa1200690

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 anti-tumor activity. Cancer Immunol Immunother 56:1897–1910. doi:10.1007/s00262-007-0332-1

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Grant support was provided by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. The authors thank Debra Weingarten for her editorial assistance in the preparation of this manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, Bethesda, MD, 20892, USA

    Caroline Jochems, Jo A. Tucker, Kwong-Yok Tsang, Ravi A. Madan, James L. Gulley & Jeffrey Schlom

  2. Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Ravi A. Madan, William L. Dahut & James L. Gulley

  3. Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    David J. Liewehr & Seth M. Steinberg

Authors
  1. Caroline Jochems
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jo A. Tucker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kwong-Yok Tsang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ravi A. Madan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William L. Dahut
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David J. Liewehr
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seth M. Steinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. James L. Gulley
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jeffrey Schlom
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey Schlom.

Additional information

James L. Gulley and Jeffrey Schlom have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jochems, C., Tucker, J.A., Tsang, KY. et al. A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates. Cancer Immunol Immunother 63, 407–418 (2014). https://doi.org/10.1007/s00262-014-1524-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-014-1524-0

Keywords

Search

Navigation