Bavarian Nordic’s Prostvac-VF vaccine extends life-time in prostate cancer patients

Prostvac-VF, a therapeutic vaccine to treat prostate cancer by Bavarian Nordic, has been found prolonging the survival of patients with metastatic cancer.

Prostvac-VF vaccine is a combination of two weakened poxviruses that have been genetically programmed to produce slightly irregular versions of prostate specific antigen (PSA) — a protein on the surface of prostate cells that is abnormal in many prostate cancers — and three costimulatory molecules that spur the immune system to a more vigorous attack on tumor cells.

Data from a clinical trial found that patients with metastatic prostate cancer who received Prostvac-VF vaccine lived substantially longer than patients who received a dummy vaccine.

Researchers at Dana-Farber Cancer Institute and affiliated organizations conducted a randomized phase II study involved the Prostvac-VF vaccine.

The double-blinded trial included 125 patients with metastatic prostate cancer who did not respond to standard, hormone-lowering therapy.

Eighty-two of the participants received the vaccine and 40 received a placebo.

At the three-year point after the study, 30 percent of the Prostvac-VF vaccine patients were alive, versus 17 percent of the control group.

The median survival of the vaccine group was 24.5 months, compared to 16 months for the control group, an 8.5-month increase.

Patients tolerated the vaccine well; only a small number experienced side effects such as fatigue, fevers, and nausea.

“Although this study is relatively small, it offers encouraging evidence of a clinically meaningful benefit from this vaccine approach,” stated principal investigator and lead author Philip Kantoff, MD, of Dana-Farber.

The findings of the study will be published by the Journal of Clinical Oncology.

A phase III trial using Prostvac-VF vaccine in about 600 patients to further evaluate the vaccine’s effectiveness will be initiated soon.

Prostvac-VF is administered subcutaneously and induces a specific, targeted immune response that attacks the cancerous cells in the prostate.

Prostvac-VF is a sequentially dosed combination of two different Poxviruses which each encode prostate specific antigen (PSA) plus three immune enhancing co-stimulatory molecules, B7.1, ICAM-1, and Lfa-3 (TRICOM).

The first Poxvirus is Vaccinia-PSA-TRICOM, which is replication competent and is good for immune priming. The second Poxvirus is Fowlpox-PSA-TRICOM, a non-replicating virus, which is good for repetitive immune boosting.

Prostvac-VF is given as monthly injections starting with a Vaccinia-PSA-TRICOM priming dose and followed by 6 monthly Fowlpox-PSA-TRICOM boosts.

Prostvac-VF is a drug-like biological therapy, which has gone through several generations of improvements, and multiple clinical trials.

Prostvac-VF targets a unique cancer cell antigen, i.e. PSA, rarely present on normal cells. PSA can be found circulating in the blood, as well as on prostate cancer cells.

PSA generally is present in small amounts in men who do not have cancer, but the quantity of PSA generally rises as prostate cancer develops. The higher a man’s PSA level is, the more likely it is that cancer is present, but there are many other possible reasons for an elevated PSA level.

Prostvac-VF uses a tumor-associated antigen which is more immunogenic, or more likely to cause an immune response, because Bavarian Nordic altered its amino acid structure slightly.

Prostvac-VF has encoded a PSA sequence which has a single alteration in HLA-A2 epitope at position 155.

Poxviruses efficiently infect a wide range of host cells and confer high level gene expression of transgenic PSA. The inclusion of TRICOM further increases immunogenicity of vaccination, where increases in number and particularly avidity of T-cell responses have been shown.

Prostvac-VF is being developed in collaboration with the National Cancer Institute (NCI) of the United States, under a formal collaborative research and development agreement (CRADA)

Bavarian Nordic is a leading industrial biotechnology company developing and producing novel vaccines.

The company’s pipeline is focused in the three areas; biodefence, cancer and infectious diseases, and includes seven development programmes.

Two programmes are ready for Phase III: Imvamune, a third-generation smallpox vaccine is being developed under a contract with the US government, and Prostvac.