Immunotherapy of Metastatic Prostate Cancer Using Dendritic Cells Pulsed with Normal Prostate Tissue Antigens
Final rept. 1 Sep 1998-28 Feb 2001
DUKE UNIV DURHAM NC
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The focus of this grant is to develop a vaccination strategy for patients with metastatic prostate cancer using DC-based vaccines loaded with normal prostate tissue-derived antigens. Having established a TRAMP colony, protocols for measuring diseases progression in the TRAMP mice we encountered initially two setbacks The TRAMP colony was severely decimated due to viral infection and generation of dendritic cells was compromised due to lack of access to a critical reagent, GM-CSF. In response to these setbacks we have regenerated the TRAMP colony and developed a GM-CSF producing cell line as a source of GM-CSF. Furthermore we have improved murine DC generation by elimination exposure to foreign substances antigens-by replacing FCS with autologous murine serum in a new media, NB 104-a significant advance in murine DC culture. We also developed a novel and apparently powerful vaccination strategy consisting of immunizing mice intradermally with lipid complexed RNA. Two large experiments in the TRAMP model are currently underway-to be completed and analyzed March-April-evaluating the use of normal prostate antigens as well as p53, a prototype for a specific tumor antigen. Successful demonstration of protective immunity in TRAMP mice will trigger preclinical studies in human prostate cancer followed by clinical trials in cancer patients.
- Medicine and Medical Research