PROSTVAC

Prostvac
Vaccine description
Target disease Prostate cancer
Type ?
Clinical data
Routes of
administration		 subcutaneous injection
Identifiers
PubChem SID 534055
ChemSpider none

PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) is a cancer immunotherapy candidate in clinical development by Bavarian Nordic for the treatment of metastatic castration-resistant prostate cancer (mCRPC). PROSTVAC is 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 poxviruses to express PSA, along with 3 immune-enhancing costimulatory molecules collectively designated as TRICOM (LFA-3, ICAM-1, and B7.1).[1] 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 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.

Clinical development

PROSTVAC is being developed in partnership with the National Cancer Institute under a formal Collaborative 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).[2] 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 study’s secondary endpoint demonstrated that patients who received PROSTVAC had a median overall survival that was 8.5 months longer than the control group (25.1 versus 16.6 months) and a 44% reduction in the risk of death (stratified log-rank P=.0061). PROSTVAC was generally well tolerated, with the most common side effects including injection site reactions, fever, fatigue, and nausea.[3]

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[4] (e.g. androgen inhibitors), radiopharmaceuticals[5] and immune checkpoint inhibitors[6][7] in the treatment of prostate cancer.

References

  1. ↑ "Survival Benefit Propels Prostate Cancer Vaccine to Phase III Trial". OncLive. Retrieved 31 October 2014.
  2. ↑ "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)". Clinicaltrials.gov. Retrieved 31 October 2014.
  3. ↑ 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 (7): 1099–105. doi:10.1200/JCO.2009.25.0597. PMC 2834462. PMID 20100959.
  4. ↑ Ardiani A, Gameiro SR, Kwilas AR, Donahue RN, Hodge JW (2014). "Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway". Oncotarget 5 (19): 9335–48. PMID 25344864.
  5. ↑ Heery C, Madan RA, et al. "A phase II randomized clinical trial of samarium-153 EDTMP (Sm-153) with or without PSA-tricom vaccine in metastatic castration-resistant prostate cancer (mCRPC) after docetaxel.". American Society of Clinical Oncology. Retrieved 3 November 2014.
  6. ↑ 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". The Lancet Oncology 13 (5): 501–8. doi:10.1016/S1470-2045(12)70006-2.
  7. ↑ Jochems C, Tucker JA, Tsang KY, Madan RA, Dahut WL, Liewehr DJ, Steinberg SM, Gulley JL, Schlom J. (2014). "A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates". Cancer Immunol Immunother. 63 (4): 407–18. doi:10.1007/s00262-014-1524-0. PMID 24514956.


This article is issued from Wikipedia - version of the Thursday, November 19, 2015. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.