Re: Interdisciplinary Critique of Sipuleucel-T as Immunotherapy in Castration-Resistant Prostate Cancer

Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215. .
Journal of the National Cancer Institute (Impact Factor: 12.58). 07/2012; 104(14):1107-9; author reply 1109-12. DOI: 10.1093/jnci/djs279
Source: PubMed
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Available from: Paul F Schellhammer, Nov 16, 2015
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    ABSTRACT: Sipuleucel-T is an autologous cellular immunotherapy approved by the US Food and Drug Administration for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Its mechanism of action is based on stimulation of the patient's own immune system to target prostate cancer. Peripheral blood mononuclear cells, including antigen-presenting cells and T cells, are obtained from patients via leukapheresis and treated ex vivo with PA2024, a fusion protein consisting of prostatic acid phosphatase/granulocyte-macrophage colony-stimulating factor antigen. Data relating to the potential pharmacodynamic biomarkers associated with sipuleucel-T activity are reviewed, as well as considerations for patient selection and for sequencing sipuleucel-T with other prostate cancer treatments. Possible directions for future development are also discussed, including treatment of less advanced prostate cancer populations, combination treatment, and immune modulation. Data from three randomized, double-blind, placebo-controlled phase III clinical trials of sipuleucel-T in patients with metastatic castration-rresistant prostate cancer have shown improvement in overall survival vs control. Here, we review its developing role in prostate cancer therapy and future directions for development. There is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.
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    ABSTRACT: Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that use the immune system, including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, whereas the vaccine PSA-TRICOM and the immune-checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short-term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth-moderating effects of these treatments, which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason, the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune-regulatory mechanisms mediated by the molecules cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter's clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer.
    Full-text · Article · Jan 2013 · The Cancer Journal
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    ABSTRACT: In 2004, the chemotherapy agent docetaxel was approved for the treatment of metastatic prostate cancer. Although it has taken almost a decade, significant new advances have been made in this area, including the clinical development of modern hormonal therapies, such as abiraterone and enzalutamide, and immunotherapies, such as sipuleucel-T, all of which have improved survival in metastatic prostate cancer. These agents have not only provided new therapeutic options for patients with advanced disease, they have also spurred research in both androgen receptor-targeting therapy and immunotherapy. Future trials will focus on the optimal sequence of these and other emerging therapies, with the aim of using these treatments earlier in the disease course (including the adjuvant setting) to enhance clinical benefit and potentially increase the cure rate for prostate cancer.
    No preview · Article · Aug 2013 · Future Oncology
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