Immunotherapy of Metastatic Prostate Cancer Using Dendritic Cells Pulsed with Normal Prostate Tissue Antigens

摘要

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.