Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors.
ISBN or ISSN
The Journal of clinical investigation
Publication Date / Copyright Date
American Society for Clinical Investigation
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.
Medicine and Health Sciences
Cancer Vaccines, Dendritic Cells, Humans, Immunotherapy, Active, Male, Prostate-Specific Antigen, Prostatic Neoplasms, RNA, Messenger, Safety, T-Lymphocytes, Cytotoxic, Transfection, Transplantation, Autologous
Heiser, Axel; Coleman, Doris; Dannull, Jens; Yancey, Donna; Maurice, Margaret A; Lallas, Costas D; Dahm, Philipp; Niedzwiecki, Donna; Gilboa, Eli; and Vieweg, Johannes, "Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors." (2002). NSU-MD Faculty Articles. 24.