A xenogeneic PSMA DNA vaccine for patients (pts) with non-castrate metastatic (NCMPC) and castrate metastatic prostate cancer (CMPC)—A phase I trial of proof of principle

Abstract

3073 Background: Prostate Specific Membrane Antigen (PSMA) represents a target for both primary and metastatic prostate cancer and an anti-angiogenic approach for other solid tumors. Antitumor effects in PC have been observed using autologous dendritic cells pulsed with PSMA peptides. This is a pilot phase I trial of vaccination with a DNA encoding PSMA in patients with PC. The objective was to determine the safety and immunogenicity of vaccination with the genes encoding for mouse and human PSMA in patients with recurrent disease. The hypothesis was that xenogeneic DNA encoding a xenogeneic homologous antigen was a more potent immunogen than self DNA. Methods: Thirty-six HLA-A0201+ pts with either NCMPC or CMPC were randomly assigned to vaccination with either xenogeneic (mouse) or human (self) PSMA DNA delivered i.m. via a high pressure delivery system at 100μg, 1,500μg or 4,000μg every 3 weeks for 3 immunizations. Those pts randomized initially to receive human PSMA DNA received 3 immunizations with mouse PSMA DNA at three week intervals. Sera and peripheral blood mononuclear cells were analyzed for humoral and T cell responses Results: Twenty-nine of 36 pts were evaluable having received all six vaccines. Nine remain active without disease progression or significant change in PSA logslope. One of 6 pts treated at the 4,000μg cohort has been followed by > 92 weeks; at the 1,500μg cohort 1 of 2 pt has been monitored for > 110 weeks; and 1 pt at the 100μg dose has remained on study for > 169 weeks. No high titer antibodies against PSMA were detected by ELISA or FACS against 3T3 fibroblasts transduced to express PSMA. Conclusions: The vaccine was safe at all dose levels without evidence of autoimmune reactivity. While antibodies against PSMA were not detected, studies are ongoing to examine T cell responsiveness. The majority of pts who remain on study were treated at 4,000μg dose level which appears to be the optimal dose. Supported by The Prostate Cancer Foundation and MSKCC Prostate Cancer SPORE No significant financial relationships to disclose.