BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: There is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.
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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: There is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.
Authors: Catherine H Marshall; Wei Fu; Hao Wang; Jong Chul Park; Theodore L DeWeese; Phuoc T Tran; Daniel Y Song; Serina King; Michaella Afful; Julia Hurrelbrink; Charlotte Manogue; Patrick Cotogno; Nancy P Moldawer; Pedro C Barata; Charles G Drake; Edwin M Posadas; Andrew J Armstrong; Oliver Sartor; Emmanuel S Antonarakis Journal: Clin Cancer Res Date: 2021-01-15 Impact factor: 13.801