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RNA Transfected Dendritic Cell Vaccines: Preclinical and Clinical Results
Dendritic cells (DC) generated from peripheral blood monocytic cells (PBMC) of prostate cancer patients and transfected with PSA-RNA are remarkably effective in stimulating potent T cell mediated anti-tumor immunity in vitro. We have performed a phase I clinical trial designed to evaluate the safety and bioactivity of the DC vaccine in 14 patients with metastatic, hormone-refractory prostate cancer. The demonstration of successful CTL generation in prostate cancer patients associated with significant impact on surrogate clinical endpoints in some patients provides a scientific rationale for further trials administering PSA RNA transfected DC vaccines in a minimal residual disease setting. The clinical and immunological experience from these trials is discussed, including the following:

    • Outcomes when dendritic cells were generated under clinical conditions from leukapheresis derived PBMC and were transfected with "naked" PSA RNA
    • Evaluations of patients who received 3 vaccinations through an iv/id route and were evaluated for toxicity as well as for immunological and clinical responses
    • Bioactivity levels of the vaccine when induction of primary, PSA specific CD8+ T cell responses were consistently measured from peripheral blood of all patients enrolled among all dose levels
    • Vaccination was further associated with a significant decrease of the serum PSA slope profiles (in 5 of 7 evaluable patients) as well as with rapid clearance of circulating tumor cells from peripheral blood in some of the immunological responders

Johannes Vieweg, MD
Assistant Professor of Urology and Immunology
DUKE UNIVERSITY MEDICAL CENTER