Clinical Efficacy of TroVax in the Treatment of Progressive Castration-resistant Prostate Cancer

Abstract

With approximately 240,890 new cases expected in 2011, prostate cancer remains the leading cause of non-melanoma cancer deaths in men. Immunotherapies using viral vector-based delivery systems targeting tumor-specific antigens are being studied. Viral vector-based delivery systems present tumor-targeted antigens (TAAs) to the immune system while breaking self-tolerance. Modified vaccinia ankara has been combined with the oncofetal antigen 5T4 to create TroVax for the treatment of castration-resistant prostate cancer (CRPC). The 5T4 antigen is highly expressed in a large number of carcinomas, including prostate cancer, but is rarely expressed in healthy tissue. TroVax has been demonstrated to be safe and highly immunogenic, both as monotherapy and in combination with other standard of care therapies in colorectal, renal cell, and prostate cancer. With minimal side effects and the ability to produce a strong immunogenic response, TroVax (MVA-5T4) is a viable addition to the treatment of prostate cancer.

Clinical development of Modified Vaccinia virus Ankara vaccines

“…No serious adverse events were reported, the majority of the patients developed antibody and cellular responses to 5T4, and these responses correlated with clinical benefit, with tumor regression observed in some cases. TroVax has also been evaluated in clinical trials for treatment of castration resistant prostate cancer [59] and a phase III trial for renal carcinoma [60] in which no efficacy was observed. Attention is now focused on identifying subgroups of patients who may benefit from therapy with TroVax [61].…”

Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors

“…For example, vaccines can be used to train the immune system to selectively destroy cancer cells. Unfortunately, the responses vaccines elicit may require months to mature and are usually insufficient to control advanced disease (2)(3)(4)(5). In an effort to increase vaccine potency, various adjuvant compounds that stimulate tumor antigen uptake and cross-priming of naive T cells have been developed, and an understanding of innate signaling mechanisms has made it possible to rationally design more precise immunostimulants for treating cancer.…”

Systematically understanding the immunity leading to CRPC progression

“…To date, immunotherapy represents an appealing option in prostate cancer treatment [12]. The FDA-approved vaccine (sipeucel-T [13]) and PD-1 inhibitor (e.g., pembrolizumab [14]) have been used to treat advanced PCa in clinical trials. However, recent phase III trials showed multiple failures of immunotherapy in PCa [15–18].…”