Prostvac

Last updated
Prostvac
Vaccine description
Target Prostate cancer
Clinical data
Routes of
administration 		subcutaneous injection
Identifiers
CAS Number
PubChem SID
ChemSpider
  • 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).

Contents

PROSTVAC utilizes recombinant 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. [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.[ citation needed ]

Clinical development

PROSTVAC is being developed in partnership with the National Cancer Institute under a formal 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). [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 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. [3] PROSTVAC was generally well tolerated, with the most common side effects including injection site reactions, fever, fatigue, and nausea. [4]

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 [5] [6] in the treatment of prostate cancer.

Commercialization

In 2015, Bristol-Myers Squibb obtained from Bavarian Nordic an "exclusive option to license and commercialize Prostvac". [7] Under a separate agreement, Bavarian Nordic would "undertake the future commercial manufacturing of Prostvac". [7]

Related Research Articles

<span class="mw-page-title-main">Prostate cancer</span> Male reproductive organ cancer

Prostate cancer is the uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Early prostate cancer usually causes no symptoms. As the tumor grows, it can damage nearby organs causing erectile dysfunction, blood in the urine or semen, and trouble urinating. Some tumors eventually spread to other areas of the body, particularly the bones and lymph nodes. There, tumors cause severe bone pain, leg weakness or paralysis, and eventually death.

A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

<span class="mw-page-title-main">Ipilimumab</span> Pharmaceutical drug

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

<span class="mw-page-title-main">DU145</span>

DU145 (DU-145) is a human prostate cancer cell line. DU145, PC3, and LNCaP are considered to be the standard prostate cancer cell lines used in therapeutic research.

<span class="mw-page-title-main">Satraplatin</span> Chemical compound

Satraplatin is a platinum-based antineoplastic agent that was under investigation as a treatment of patients with advanced prostate cancer who have failed previous chemotherapy. It has not yet received approval from the U.S. Food and Drug Administration. First mentioned in the medical literature in 1993, satraplatin is the first orally active platinum-based chemotherapeutic drug; other available platinum analogues—cisplatin, carboplatin, and oxaliplatin—must be given intravenously.

<span class="mw-page-title-main">Enzalutamide</span> Antiandrogen medication used in treatment of prostate cancer

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.

Radium-223 is an isotope of radium with an 11.4-day half-life. It was discovered in 1905 by T. Godlewski, a Polish chemist from Kraków, and was historically known as actinium X (AcX). Radium-223 dichloride is an alpha particle-emitting radiotherapy drug that mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover. The principal use of radium-223, as a radiopharmaceutical to treat metastatic cancers in bone, takes advantage of its chemical similarity to calcium, and the short range of the alpha radiation it emits.

James L. Gulley is an American cancer researcher and the Director of the Medical Oncology Service at National Cancer Institute.

William K. Oh, is an American medical oncologist, academic and industry leader and expert in the management of genitourinary malignancies, including prostate, renal, bladder and testicular cancers.

<span class="mw-page-title-main">Cabazitaxel</span> Chemical compound

Cabazitaxel, sold under the brand name Jevtana, is a semi-synthetic derivative of a natural taxoid. It is a microtubule inhibitor, and the fourth taxane to be approved as a cancer therapy.

Sipuleucel-T, sold under the brand name Provenge, developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer (CaP). It is an autologous cellular immunotherapy.

<span class="mw-page-title-main">Tasquinimod</span> Chemical compound

Tasquinimod is an experimental drug currently being investigated for the treatment of solid tumors. Tasquinimod has been mostly studied in prostate cancer, but its mechanism of action suggests that it could be used to treat other cancers. Castration-resistant prostate cancer (CRPC), formerly called hormone-resistant or hormone-refractory prostate cancer, is prostate cancer that grows despite medical or surgical androgen deprivation therapy. Tasquinimod targets the tumor microenvironment and counteracts cancer development by inhibiting angiogenesis and metastasis and by modulating the immune system. It is now in phase III development, following successful phase II trial outcomes.

Eftilagimod alpha is a large-molecule cancer drug being developed by the clinical-stage biotechnology company Immutep. Efti is a soluble version of the immune checkpoint molecule LAG-3. It is an APC Activator used to increase an immune response to tumors, and is administered by subcutaneous injection. Efti has three intended clinical settings:

Darolutamide, sold under the brand name Nubeqa, is an antiandrogen medication which is used in the treatment of non-metastatic castration-resistant prostate cancer in men. It is specifically approved to treat non-metastatic castration-resistant prostate cancer (nmCRPC) in conjunction with surgical or medical castration. The medication is taken by mouth twice per day with food.

Abituzumab is a humanized IgG2 monoclonal antibody (mAb) targeted at CD51 currently in development by Merck KGaA Darmstadt, Germany in an attempt to prevent bone lesion metastases in castration-resistant prostate cancer.

<span class="mw-page-title-main">Ralaniten acetate</span> Chemical compound

Ralaniten acetate is a first-in-class antiandrogen that targets the N-terminal domain (NTD) of the androgen receptor (AR) developed by ESSA Pharmaceuticals and was under investigation for the treatment of prostate cancer. This mechanism of action is believed to allow the drug to block signaling from the AR and its splice variants. EPI-506 is a derivative of bisphenol A and a prodrug of ralaniten (EPI-002), one of the four stereoisomers of EPI-001, and was developed as a successor of EPI-001. The drug reached phase I/II prior to the discontinuation of its development. It showed signs of efficacy in the form of prostatic specific antigen (PSA) decreases (4–29%) predominantly at higher doses (≥1,280 mg) in some patients but also caused side effects and was discontinued by its developer in favor of next-generation AR NTD inhibitors with improved potency and tolerability.

The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for cancer patients.

A therapeutic vaccine is a vaccine which is administered after a disease or infection has already occurred. A therapeutic vaccine works by activating the immune system of a patient to fight an infection. A therapeutic vaccine differs from a prophylactic vaccine in that prophylactic vaccines are administered to individuals as a precautionary measure to avoid the infection or disease while therapeutic vaccines are administered after the individual is already affected by the disease or infection. A therapeutic vaccine fights an existing infection in the body rather than immunizing the body for protection against future diseases and infections. Therapeutic vaccines are mostly used against viral infections. Patients affected with chronic viral infections are administered with therapeutic vaccines, as their immune system is not able to produce enough efficient antibodies.

Lutetium (<sup>177</sup>Lu) vipivotide tetraxetan Radiopharmaceutical medication

Lutetium (177Lu) vipivotide tetraxetan, sold under the brand name Pluvicto, is a radiopharmaceutical medication used for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy.

References

  1. ↑ "Survival Benefit Propels Prostate Cancer Vaccine to Phase III Trial". OncLive. June 2013. 2 (3). 3 July 2013. Retrieved 2014-10-31.
  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. ↑ 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
  4. ↑ 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.
  5. ↑ 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. PMC   6359905 . PMID   22326924.
  6. ↑ 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. PMC   6314199 . PMID   24514956.
  7. 1 2 Staff (1 April 2015). "Bavarian Nordic Could Reap $975M in Prostate Cancer Deal with BMS". Genetic Engineering & Biotechnology News (Paper). 35 (7): 12. Retrieved 2016-06-12.


Syringe with Green Fluid.jpg

This article about vaccines or vaccination is a stub. You can help Wikipedia by expanding it.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.