Vaccinia-Based Vaccine Shows Promise for Treating Prostate Cancer

Vaccinia-Based Vaccine Shows Promise for Treating Prostate Cancer.

Researchers from National Cancer Institute have reported progress in the development of a recombinant vaccinia-based vaccine for the treatment of hormone-refractory prostate cancer in combination with radiation therapy or anti-androgen therapy.[i][ii]

The prostate is a gland of the male reproductive system, which is responsible for producing fluid that transports the sperm during male ejaculation. Prostate cancer is a disease in which cancer cells form in the tissues of the prostate. After skin cancer, prostate cancer is the most common form of cancer diagnosed in men. During the past 20 years, however, overall survival rates for all stages of prostate cancer have improved dramatically. Current treatment options for prostate cancer include watchful waiting, surgery, chemotherapy, radiation, or hormonal therapy. Hormonal therapy is designed to lower the presence or block the effects of testosterone, which can stimulate the growth of hormone-dependent types of prostate cancer. Some types of prostate cancers can become resistant to hormonal therapy, requiring a different approach; this is known as hormone refractory or resistant prostate cancer.

There has been much progress in recent years in developing vaccines for the treatment of cancer; however, none have been approved by the U.S. Food and Drug Administration at this time. Vaccines are biologics that stimulate the immune system to destroy cancer cells in the body. There have been several different vaccine approaches for the treatment of prostate cancer; the most advanced studies involve a dendritic cell vaccine called Provenge®.[iii] Dendritic cells are antigen-presenting cells that have been incorporated into several vaccine strategies over the past decade. Dendritic cells are CD34+ cells collected from the peripheral blood, usually after the administration of Neupogen®. Provenge is a prototype vaccine that incorporates a specific antigen and a proprietary fusion protein of GM-CSF, which are loaded onto autologous expanded antigen-presenting cells (dendritic cells). The procedure requires mobilization and collection of PBSC for isolation of dendritic cells.

The vaccine used in the current studies consisted of recombinant vaccinia viruses containing the PSA and B7.1 co-stimulatory genes and avipox-PSA as boosters. In the first study, 30 patients with localized prostate cancer were randomly allocated to receive radiation therapy alone or radiation therapy with vaccination. There were eight vaccine injections in this study. Seventeen of 19 patients assigned to vaccine received all eight doses. Thirteen of these 17 patients had significant increases in PSA-specific T cells compared to none in the radiation alone group. This study showed that the vaccine could be given safely and that specific T-cell responses were achieved in the majority of patients. It will obviously take a long follow-up to determine if the vaccine was effective in this group of patients.

In the second study, 42 patients with hormone-refractory prostate cancer were randomized to receive either vaccination or anti-hormonal therapy with nilutamide (Anandron®). If, after six months of treatment, the patients had no metastasis and their PSA continued to rise, they could then receive a combination of both treatments. When the study was completed, three patients who had received Anandron had been removed from the study due to moderate side effects. No significant side effects were observed among the patients treated with vaccine. The vaccinated group of patients, treatment remained effective for 9.9 months versus 7.6 months in the Anandron treated group. Both groups showed a high rate of decrease in PSA velocity with initial therapy: 62% in the vaccine group and 76% in the Anandron group. After six months, eight of the patients in the Anandron group had vaccine added to treatment, which resulted in treatment failure (time when treatment stopped working) in 5.2 months. Patients receiving Anandron followed by vaccine had a median time on study of 15.9 months. Twelve patients in the vaccine group received Anandron with a median time to disease progression of 13.9 months and had a median of 25.9 months of therapy.

It appeared from this preliminary study that combined vaccine and anti-androgen therapy was the most effective approach for future studies. These two studies suggest that a vaccinia-based vaccine has activity and little toxicity in patients with prostate cancer. These studies suggest a future role for vaccine in combination with conventional treatments. Patients with prostate cancer may wish to discuss participation in ongoing vaccine trials.

References:

[i] Gulley JL, Arlen PM, Bastian A, et al. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clinical Cancer Research. 2005;11:3353-3362.

[ii] Arlen PM, Gulley JL, Todd N, et al. Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer. Journal of Urology. 2005;174:539-546.

[iii] Small EJ, Schellhammer PF, Higano CS, et al. Results of a placebo-controlled phase III trial of immunotherapy with APC801 for patients with hormone refractory prostate cancer (HRPC). Proceedings of the 41st Annual Meeting of the American Society of Clinical Oncology; Abstract #4500.

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