Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors.
Autologous dendritic cells (DCs) transfected with mRNA encoding prostate-specific antigen (PSA) are able to stimulate potent, T cell-mediated antitumor immune responses in vitro. A phase I trial was performed to evaluate this strategy for safety, feasibility, and efficacy to induce T cell responses against the self-protein PSA in patients with metastatic prostate cancer. In 13 study subjects, escalating doses of PSA mRNA-transfected DCs were administered with no evidence of dose-limiting toxicity or adverse effects, including autoimmunity. Induction of PSA-specific T cell responses was consistently detected in all patients, suggesting in vivo bioactivity of the vaccine. Vaccination was further associated with a significant decrease in the log slope PSA in six of seven subjects; three patients that could be analyzed exhibited a transient molecular clearance of circulating tumor cells. The demonstration of vaccine safety, successful in vivo induction of PSA-specific immunity, and impact on surrogate clinical endpoints provides a scientific rationale for further clinical investigation of RNA-transfected DCs in the treatment of human cancer.
Heiser
Axel
A
Cancer Immunotherapy Program, Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Coleman
Doris
D
Dannull
Jens
J
Yancey
Donna
D
Maurice
Margaret A
MA
Lallas
Costas D
CD
Dahm
Philipp
P
Niedzwiecki
Donna
D
Gilboa
Eli
E
Vieweg
Johannes
J
D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics*; D012449:Safety; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014182:Transplantation, Autologous
D019496:Cancer Vaccines; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen