Promising Novel Immunotherapies and Combinations for Prostate Cancer

Abstract

The field of therapeutic cancer vaccines is currently in a state of active preclinical and clinical investigation, and certain novel therapies involving tumor immunotherapy have recently come to the forefront of prostate cancer research. While no therapeutic cancer vaccine has yet been approved by the US FDA, recent findings have demonstrated that new paradigms of combination therapies involving vaccines, employed in clinical trials with appropriate design and end points, may ultimately lead to cancer vaccines being used to treat various malignancies. Several characteristics of prostate cancer make it an ideal target for immunotherapy. Its relative indolence allows sufficient time to generate immune responses, which usually take weeks or months to mount. In addition, prostate cancer-associated antigens direct the immune response to prostate cancer cells, thus sparing normal tissue. This review focuses on the future of promising new vaccines and novel perspectives in the treatment of prostate cancer.

Unleashing the therapeutic potential of human kallikrein-related serine proteases

“…The US regulatory approval of sipu leucel-T (Provenge; Dendreon Corporation), a prostatic-acid-phosphatase-based vaccine for the treatment of asymptomatic androgen-resistant prostate cancer, demonstrated the therapeutic potential of immunotherapy in treating prostate cancer 207,208 . The identification of the patient groups that are most likely to benefit from such regimens, and the optimization of the timing of immunotherapy with regard to existing treatment regimens (for example, before or after androgen deprivation) are areas of intense ongoing research [209][210][211][212][213] .…”

Modulation of bone morphogenic protein signaling in T-cells for cancer immunotherapy

“…Increased understanding how adaptive T-cell functions are regulated in tumors has already led to effective cancer immunotherapies (Pardoll, 2012). It has also become apparent that not only cancer immunotherapy but also traditional cancer treatments, relying on surgical tumor removal, chemo- and/or radiation therapy depend on effective stimulation of the immune system to completely eradicate tumor cells (Arlen et al, 2009; Gray et al, 2009; Muranski and Restifo, 2009). Immune response against tumor antigens, that frequently are self-antigens, depends on overcoming mechanisms of peripheral tolerance and is often compromised by inefficient T-cell activation or anergy induction.…”

Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination

“…Docetaxel-based therapy has been shown to improve survival by approximately 2–3 months in this setting [2]. Immunotherapeutic approaches using peptide- or dendritic cell-based vaccines and poxviral-based vaccines have shown evidence of clinical benefit [3]. A recently reported phase III trial of sipuleucel-T vaccine in patients with metastatic castration-resistant PCa (mCRPC) was the first trial with overall survival (OS) as the primary endpoint to demonstrate a statistically significant improvement in OS with a cell-based therapeutic vaccine [4].…”