Mayer Fishman1. 1. Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL 33612, USA. Mayer.Fishman@moffitt.org
Abstract
BACKGROUND: Northwest Therapeutics' DCvax-prostate consists of autologous dendritic cells (DCs) loaded with prostate-specific membrane antigen (PSMA) peptides, administered intravenously. Phase I-II testing, a decade ago, showed clinical benefit and immunological response in some patients. More recently DCvax brain, a product using a similar DC platform showed encouraging Phase I-II results and sipleucel-T, a prostatic acid phosphatase (PAP)-directed DC immunotherapy had positive Phase III results. OBJECTIVE: Features of the clinical setting into which a new immunotherapy could be introduced are discussed, to refine a perspective on DCvax-prostate in the context of evolving prostate cancer therapeutics. PSMA-directed therapeutics and immune anticancer technologies are reviewed, and the clinical and immunological correlative testing of DCvax-prostate is discussed. METHODS: Clinical and preclinical data from peer-reviewed literature, meetings proceedings and manufacturer-provided information are considered. CONCLUSION: DCvax-prostate had encouraging early-phase trial results, but development and testing had stalled. As a more detailed understanding of patient-selection for capacity for anticancer immune response, the quantitation of immunological correlates, and the changing marketplace develop, it is appealing to consider a well tolerated, PSMA-directed autologous dendritic cell therapeutic product. Further clinical trial development of DCvax-prostate is warranted, and required if it is to find a relevant clinical application.
BACKGROUND: Northwest Therapeutics' DCvax-prostate consists of autologous dendritic cells (DCs) loaded with prostate-specific membrane antigen (PSMA) peptides, administered intravenously. Phase I-II testing, a decade ago, showed clinical benefit and immunological response in some patients. More recently DCvax brain, a product using a similar DC platform showed encouraging Phase I-II results and sipleucel-T, a prostatic acid phosphatase (PAP)-directed DC immunotherapy had positive Phase III results. OBJECTIVE: Features of the clinical setting into which a new immunotherapy could be introduced are discussed, to refine a perspective on DCvax-prostate in the context of evolving prostate cancer therapeutics. PSMA-directed therapeutics and immune anticancer technologies are reviewed, and the clinical and immunological correlative testing of DCvax-prostate is discussed. METHODS: Clinical and preclinical data from peer-reviewed literature, meetings proceedings and manufacturer-provided information are considered. CONCLUSION:DCvax-prostate had encouraging early-phase trial results, but development and testing had stalled. As a more detailed understanding of patient-selection for capacity for anticancer immune response, the quantitation of immunological correlates, and the changing marketplace develop, it is appealing to consider a well tolerated, PSMA-directed autologous dendritic cell therapeutic product. Further clinical trial development of DCvax-prostate is warranted, and required if it is to find a relevant clinical application.
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