View source for Prostvac

{{Short description|Prostate cancer vaccine}}
{{Drugbox
<!-- Vaccine data -->
| type = vaccine
| target = [[Prostate cancer]]
<!-- Clinical data -->
| routes_of_administration = [[subcutaneous injection]]
<!-- Identifiers -->
| CAS_number = 947602-09-7
| PubChemSubstance = 534055
| ChemSpiderID = none
}}
'''PROSTVAC''' (rilimogene galvacirepvec/rilimogene glafolivec) is a [[cancer immunotherapy]] candidate in clinical development by [[Bavarian Nordic]] for the treatment of all [[prostate cancer]] although clinical trials are focusing on more advanced cases of metastatic castration-resistant [[prostate cancer]] (mCRPC). PROSTVAC is a [[vaccine]] designed to enable the immune system to recognize and attack prostate cancer cells by triggering a specific and targeted T cell [[immune response]] to cancer cells that express the tumor-associated antigen [[prostate-specific antigen]] (PSA).
PROSTVAC utilizes recombinant [[Poxviridae|poxviruses]] that express PSA, along with 3 immune-enhancing costimulatory molecules collectively designated as TRICOM ([[LFA-3]], [[ICAM-1]], and [[B7.1]]) to stimulate an immune response.<ref>{{cite journal|url=http://www.onclive.com/publications/urologists-in-cancer-care/2013/june-2013/Survival-Benefit-Propels-Prostate-Cancer-Vaccine-to-Phase-III-Trial|title=Survival Benefit Propels Prostate Cancer Vaccine to Phase III Trial|date=3 July 2013|journal=OncLive|series=June 2013 |volume=2 |issue=3 |access-date=2014-10-31}}</ref> Treatment is initiated by subcutaneous administration of a priming dose of [[vaccinia]] encoding PSA-TRICOM, followed by 6 subsequent boosting doses of [[fowlpox]] encoding the same PSA-TRICOM [[Gene cassette|cassette]]. Using this heterologous prime-boost dosing regimen, the immune system becomes focused on inducing PSA-specific T cell responses, designed to kill tumor cells expressing PSA.{{cn|date=November 2020}}
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== Clinical development ==
PROSTVAC is being developed in partnership with the [[National Cancer Institute]] under a formal [[Cooperative research and development agreement|Cooperative Research and Development Agreement]] and has been the subject of multiple ongoing and completed clinical studies, including the global Phase 3 PROSPECT study underway in patients with asymptomatic or minimally symptomatic metastatic prostate cancer (mCRPC).<ref>{{cite web|url=http://clinicaltrials.gov/ct2/show/NCT01322490|title=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)|work=Clinicaltrials.gov|access-date=31 October 2014}}</ref> This Phase 3 study is designed to validate positive clinical data from a randomized, controlled, double-blind Phase 2 clinical trial that enrolled 125 minimally symptomatic mCRPC patients. The Phase 2 study's secondary endpoint demonstrated that patients who received PROSTVAC had a median overall survival that was 9.9 months longer than the control group (26.2 versus 16.3 months)(p. < .01) and a reduction in the risk of death.<ref>Revised Overall Survival Analysis of a Phase II, Randomized, Double-Blind, Controlled Study of PROSTVAC in Men With Metastatic Castration-Resistant Prostate Cancer  Philip W. Kantoff, James L. Gulley, and Cesar Pico-Navarro Journal of Clinical Oncology 2017 35:1, 124-125</ref> PROSTVAC was generally well tolerated, with the most common side effects including injection site reactions, fever, fatigue, and nausea.<ref>{{cite journal|vauthors=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 |title=Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer|journal=J Clin Oncol|year=2010|volume=28|pages=1099–105|doi=10.1200/JCO.2009.25.0597|pmid=20100959|issue=7|pmc=2834462}}</ref>
Based on non-clinical data supporting the scientific rationale for combination therapy with PROSTVAC, additional clinical trials are underway to evaluate the potential clinical benefit of combining PROSTVAC with different treatment modalities such as hormonal therapies (e.g. androgen inhibitors), radiopharmaceuticals and [[immune checkpoint]] inhibitors<ref>{{cite journal|vauthors=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 |title=Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial|journal=The Lancet Oncology|year=2012|volume=13|pages=501–8|doi=10.1016/S1470-2045(12)70006-2|issue=5|pmc=6359905|pmid=22326924}}</ref><ref>{{cite journal|vauthors=Jochems C, Tucker JA, Tsang KY, Madan RA, Dahut WL, Liewehr DJ, Steinberg SM, Gulley JL, Schlom J |title=A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates|journal=Cancer Immunol Immunother|year=2014|volume=63|pages=407–18|doi=10.1007/s00262-014-1524-0|pmid=24514956|issue=4|pmc=6314199|url=https://zenodo.org/record/1232659}}</ref> in the treatment of prostate cancer.
== Commercialization ==
In 2015, [[Bristol-Myers Squibb]] obtained from [[Bavarian Nordic]] an "exclusive option to license and commercialize Prostvac".<ref name=":0">{{Cite journal|last=Staff|date=1 April 2015|title=Bavarian Nordic Could Reap $975M in Prostate Cancer Deal with BMS|url=http://gen.epubxp.com/i/480085-apr1-2015/13|journal=[[Gen. Eng. Biotechnol. News|Genetic Engineering & Biotechnology News]]|type=Paper|volume=35|issue=7|page=12|access-date=2016-06-12}}</ref>  Under a separate agreement, Bavarian Nordic would "undertake the future commercial manufacturing of Prostvac".<ref name=":0" />
==References==
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{{Vaccines}}
[[Category:Cancer vaccines]]
[[Category:Prostate cancer]]
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