Review
. 2014 Sep; 2(5):137-48.
doi: 10.1177/2051013614539478.

Therapeutic vaccines as a promising treatment modality against prostate cancer: rationale and recent advances

B Harpreet Singh 1 James L Gulley 2 
Affiliations
  • PMID: 25177493
  •     53 References
  •     8 citations

Abstract

Cancer immunotherapy was deemed the medical breakthrough of 2013, in part because it can induce a rapid, durable, self-propagating and adaptable immune response. Specifically in prostate cancer, immunotherapy has emerged as a viable and attractive treatment strategy. To date, therapeutic cancer vaccines and immune checkpoint inhibitors are the two classes of immunotherapy that have demonstrated improvements in overall survival in patients with advanced tumors. The 2010 Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A class effect of these approved immune-based therapies is a benefit in overall survival without short-term changes in disease progression, apparently due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. A growing body of evidence suggests that the ideal population for clinical trials of cancer vaccines as monotherapy is patients with lower tumor volume and less aggressive disease. Combination strategies include immunotherapy with standard therapies or with other immunotherapies. Here we review emerging data on immunotherapy for patients with prostate cancer.

Keywords: antigen cascade; antigen spreading; combination therapy; immune checkpoint inhibitor; immune intensification; immunotherapy.

Synergizing radiation therapy and immunotherapy for curing incurable cancers. Opportunities and challenges.
James W Hodge, Chandan Guha, Jacques Neefjes, James L Gulley.
Oncology (Williston Park), 2008 Sep 10; 22(9). PMID: 18777956    Free PMC article.
Review.
Age-related changes in tissue levels of prostatic acid phosphatase and prostate specific antigen.
D A Goldfarb, B S Stein, M Shamszadeh, R O Petersen.
J Urol, 1986 Dec 01; 136(6). PMID: 2430115
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Clinical safety of a viral vector based prostate cancer vaccine strategy.
Philip M Arlen, Lisa Skarupa, +15 authors, James L Gulley.
J Urol, 2007 Aug 21; 178(4 Pt 1). PMID: 17707059
T cell profiling reveals high CD4+CTLA-4 + T cell frequency as dominant predictor for survival after prostate GVAX/ipilimumab treatment.
Saskia J A M Santegoets, Anita G M Stam, +13 authors, Tanja D de Gruijl.
Cancer Immunol Immunother, 2012 Aug 11; 62(2). PMID: 22878899
Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer.
James L Gulley, Philip M Arlen, +13 authors, William Dahut.
Clin Cancer Res, 2005 May 04; 11(9). PMID: 15867235
Highly Cited.
Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer.
James L Gulley, Philip M Arlen, +17 authors, Jeffrey Schlom.
Cancer Immunol Immunother, 2009 Nov 06; 59(5). PMID: 19890632    Free PMC article.
Highly Cited.
Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial.
Paul F Schellhammer, Gerald Chodak, +3 authors, Philip W Kantoff.
Urology, 2013 Apr 16; 81(6). PMID: 23582482
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
M F Krummel, J P Allison.
J Exp Med, 1995 Aug 01; 182(2). PMID: 7543139    Free PMC article.
Highly Cited.
Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer.
Ravi A Madan, Philip M Arlen, +2 authors, James L Gulley.
Expert Opin Investig Drugs, 2009 Jun 25; 18(7). PMID: 19548854    Free PMC article.
Review.
Complete biochemical (prostate-specific antigen) response to sipuleucel-T with enzalutamide in castration-resistant prostate cancer: a case report with implications for future research.
Julie N Graff, Charles G Drake, Tomasz M Beer.
Urology, 2013 Feb 05; 81(2). PMID: 23374810    Free PMC article.
Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model.
Andressa Ardiani, Benedetto Farsaci, +5 authors, James W Hodge.
Clin Cancer Res, 2013 Sep 21; 19(22). PMID: 24048332    Free PMC article.
Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer.
Jeanny B Aragon-Ching, Kirsten M Williams, James L Gulley.
Front Biosci, 2007 Jun 16; 12. PMID: 17569623
Review.
Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade.
A A Hurwitz, B A Foster, +5 authors, J P Allison.
Cancer Res, 2000 May 16; 60(9). PMID: 10811122
Highly Cited.
Shaping and reshaping CD8+ T-cell memory.
John T Harty, Vladimir P Badovinac.
Nat Rev Immunol, 2008 Jan 26; 8(2). PMID: 18219309
Highly Cited. Review.
Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study.
S F Slovin, C S Higano, +8 authors, T M Beer.
Ann Oncol, 2013 Mar 29; 24(7). PMID: 23535954    Free PMC article.
Highly Cited.
The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing.
Mala Chakraborty, Elizabeth K Wansley, +7 authors, James W Hodge.
Clin Cancer Res, 2008 Jul 03; 14(13). PMID: 18594006    Free PMC article.
Immunotherapy for prostate cancer: recent advances, lessons learned, and areas for further research.
James L Gulley, Charles G Drake.
Clin Cancer Res, 2011 Jun 18; 17(12). PMID: 21680544    Free PMC article.
Review.
Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes.
L G Tilney, D A Portnoy.
J Cell Biol, 1989 Oct 01; 109(4 Pt 1). PMID: 2507553    Free PMC article.
Highly Cited.
Cancer vaccines: moving beyond current paradigms.
Jeffrey Schlom, Philip M Arlen, James L Gulley.
Clin Cancer Res, 2007 Jul 04; 13(13). PMID: 17606707    Free PMC article.
Review.
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L Topalian, F Stephen Hodi, +27 authors, Mario Sznol.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658127    Free PMC article.
Highly Cited.
Therapeutic vaccines for prostate cancer.
Christopher P Tarassoff, Philip M Arlen, James L Gulley.
Oncologist, 2006 May 25; 11(5). PMID: 16720845
Review.
PD-1-targeted immunotherapy: recent clinical findings.
Julie R Brahmer.
Clin Adv Hematol Oncol, 2012 Nov 29; 10(10). PMID: 23187774
Sipuleucel-T: a vaccine for metastatic, asymptomatic, androgen-independent prostate cancer.
Punam H Patel, Denise R Kockler.
Ann Pharmacother, 2007 Dec 21; 42(1). PMID: 18094343
Review.
A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer.
J P Eder, P W Kantoff, +11 authors, D W Kufe.
Clin Cancer Res, 2000 May 18; 6(5). PMID: 10815880
Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression.
Ravi A Madan, James L Gulley, Tito Fojo, William L Dahut.
Oncologist, 2010 Aug 28; 15(9). PMID: 20798195    Free PMC article.
Immunogenic cell death in cancer therapy.
Guido Kroemer, Lorenzo Galluzzi, Oliver Kepp, Laurence Zitvogel.
Annu Rev Immunol, 2012 Nov 20; 31. PMID: 23157435
Highly Cited. Review.
Promises and challenges for the development of Listeria monocytogenes-based immunotherapies.
Dirk G Brockstedt, Thomas W Dubensky.
Expert Rev Vaccines, 2008 Sep 05; 7(7). PMID: 18767955
Review.
Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial.
Ravi A Madan, Mahsa Mohebtash, +10 authors, James L Gulley.
Lancet Oncol, 2012 Feb 14; 13(5). PMID: 22326924    Free PMC article.
Highly Cited.
Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer.
Philip W Kantoff, Thomas J Schuetz, +11 authors, Wayne R Godfrey.
J Clin Oncol, 2010 Jan 27; 28(7). PMID: 20100959    Free PMC article.
Highly Cited.
Multiple costimulatory modalities enhance CTL avidity.
James W Hodge, Mala Chakraborty, +2 authors, Jeffrey Schlom.
J Immunol, 2005 May 10; 174(10). PMID: 15879092    Free PMC article.
Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy.
Wilfred D Stein, James L Gulley, +8 authors, Tito Fojo.
Clin Cancer Res, 2010 Nov 26; 17(4). PMID: 21106727    Free PMC article.
Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen.
Charles G Drake, Amy D H Doody, +12 authors, Adam J Adler.
Cancer Cell, 2005 Mar 16; 7(3). PMID: 15766662    Free PMC article.
Highly Cited.
From clinical trials to clinical practice: therapeutic cancer vaccines for the treatment of prostate cancer.
Ravi A Madan, Jeanny B Aragon-Ching, James L Gulley, William L Dahut.
Expert Rev Vaccines, 2011 Jun 23; 10(6). PMID: 21692697    Free PMC article.
Review.
Therapeutic vaccines: the ultimate personalized therapy?
James L Gulley.
Hum Vaccin Immunother, 2012 Sep 22; 9(1). PMID: 22995839    Free PMC article.
T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer.
M Mercader, B K Bodner, +10 authors, E D Kwon.
Proc Natl Acad Sci U S A, 2001 Dec 06; 98(25). PMID: 11734652    Free PMC article.
Highly Cited.
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 L Marshall, R J Hoyer, +9 authors, J Schlom.
J Clin Oncol, 2000 Dec 01; 18(23). PMID: 11099326
Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases.
D G Bostwick, A Pacelli, +2 authors, G P Murphy.
Cancer, 1998 Jun 04; 82(11). PMID: 9610707
Highly Cited.
A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates.
Caroline Jochems, Jo A Tucker, +6 authors, Jeffrey Schlom.
Cancer Immunol Immunother, 2014 Feb 12; 63(4). PMID: 24514956    Free PMC article.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing.
Mala Chakraborty, Scott I Abrams, +3 authors, James W Hodge.
Cancer Res, 2004 Jun 19; 64(12). PMID: 15205348
Highly Cited.
Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy.
Mala Chakraborty, Scott I Abrams, +4 authors, James W Hodge.
J Immunol, 2003 Jun 10; 170(12). PMID: 12794167
Highly Cited.
Purification of a human prostate specific antigen.
M C Wang, L A Valenzuela, G P Murphy, T M Chu.
Invest Urol, 1979 Sep 01; 17(2). PMID: 89106
Highly Cited.
Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
Philip W Kantoff, Celestia S Higano, +11 authors, IMPACT Study Investigators.
N Engl J Med, 2010 Sep 08; 363(5). PMID: 20818862
Highly Cited.
Pathogenicity and immunogenicity of Listeria monocytogenes small-plaque mutants defective for intracellular growth and cell-to-cell spread.
R A Barry, H G Bouwer, D A Portnoy, D J Hinrichs.
Infect Immun, 1992 Apr 01; 60(4). PMID: 1548084    Free PMC article.
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.
Alfons J M van den Eertwegh, Jurjen Versluis, +15 authors, Winald R Gerritsen.
Lancet Oncol, 2012 Feb 14; 13(5). PMID: 22326922
Highly Cited.
Therapeutic vaccines and immunotherapy in castration-resistant prostate cancer: current progress and clinical applications.
James L Gulley, Ravi A Madan, Christopher R Heery.
Am Soc Clin Oncol Educ Book, 2013 May 30;. PMID: 23714490    Free PMC article.
Review.
Technology evaluation: APC-8015, Dendreon.
Brian I Rini.
Curr Opin Mol Ther, 2002 Mar 09; 4(1). PMID: 11883698
Review.
Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death.
James W Hodge, Charlie T Garnett, +4 authors, Sofia R Gameiro.
Int J Cancer, 2013 Feb 01; 133(3). PMID: 23364915    Free PMC article.
Highly Cited.
Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer.
James Gulley, Alice P Chen, +8 authors, J Michael Hamilton.
Prostate, 2002 Sep 21; 53(2). PMID: 12242725
New therapies for castration-resistant prostate cancer.
Dan L Longo.
N Engl J Med, 2010 Sep 08; 363(5). PMID: 20818868
Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.
Julie R Brahmer, Charles G Drake, +17 authors, Suzanne L Topalian.
J Clin Oncol, 2010 Jun 03; 28(19). PMID: 20516446    Free PMC article.
Highly Cited.
Immune impact induced by PROSTVAC (PSA-TRICOM), a therapeutic vaccine for prostate cancer.
James L Gulley, Ravi A Madan, +9 authors, Jeffrey Schlom.
Cancer Immunol Res, 2014 Apr 30; 2(2). PMID: 24778277    Free PMC article.
Adding fuel to the fire: immunogenic intensification.
Geraldine O'Sullivan Coyne, James L Gulley.
Hum Vaccin Immunother, 2014 Dec 09; 10(11). PMID: 25483630    Free PMC article.
Review.
Chronic inflammation: is it the driver or is it paving the road for malignant transformation?
Kambiz Afrasiabi, Yi-Hong Zhou, Angela Fleischman.
Genes Cancer, 2015 Jul 01; 6(5-6). PMID: 26124920    Free PMC article.
Cancer prevention: state of the art and future prospects.
I Valle, D Tramalloni, N L Bragazzi.
J Prev Med Hyg, 2016 Jan 21; 56(1). PMID: 26789828    Free PMC article.
Review.
Tn-MUC1 DC Vaccination of Rhesus Macaques and a Phase I/II Trial in Patients with Nonmetastatic Castrate-Resistant Prostate Cancer.
Elizabeth Scheid, Pierre Major, +18 authors, Ronan Foley.
Cancer Immunol Res, 2016 Sep 09; 4(10). PMID: 27604597    Free PMC article.
Enzalutamide in castration-resistant prostate cancer patients with visceral disease in the liver and/or lung: Outcomes from the randomized controlled phase 3 AFFIRM trial.
Yohann Loriot, Karim Fizazi, +3 authors, Howard I Scher.
Cancer, 2016 Sep 21; 123(2). PMID: 27648814    Free PMC article.
Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer.
T J Mai, R Ma, Z Li, S C Bi.
Braz J Med Biol Res, 2016 Oct 27; 49(11). PMID: 27783810    Free PMC article.
Dissecting major signaling pathways in prostate cancer development and progression: Mechanisms and novel therapeutic targets.
Senthilmurugan Ramalingam, Vidya P Ramamurthy, Vincent C O Njar.
J Steroid Biochem Mol Biol, 2016 Aug 03; 166. PMID: 27481707    Free PMC article.
Review.
Immune Targeting of Tumor Epithelial-Mesenchymal Transition via Brachyury-Based Vaccines.
Claudia Palena, Duane H Hamilton.
Adv Cancer Res, 2015 Jul 29; 128. PMID: 26216630    Free PMC article.
Review.