A changing world for DCvax: a PSMA loaded autologous dendritic cell vaccine for prostate cancer.
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.


CONCLUSIONS
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.
Fishman
Mayer
M
Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL 33612, USA. Mayer.Fishman@moffitt.org
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000378:metabolism / Q000637:transplantation*; D017277:Drug Approval; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D014020:Tissue Extracts / Q000627:therapeutic use; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000954:Antigens, Surface; D019496:Cancer Vaccines; D014020:Tissue Extracts; C511774:sipuleucel-T; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II