Phase I trial of a PSMA DNA vaccine for patients(pts) with good risk renal cell carcinoma(RCC)

Abstract

16073 Background: Prostate Specific Membrane Antigen (PSMA) is a self antigen first identified as a marker for epithelial cells in the prostate but is expressed on the vascular endothelium of metastatic RCC. PSMA mRNA transcripts and protein expression have been seen in the endothelium of tumor-associated neovasculature of non-metastatic malignancies. No PSMA mRNA or protein expression has been found in vascular endothelial cells of corresponding benign tissues. The clinical importance of PSMA expression is supported by the observation that PSMA RNA detected by RT-PCR in the circulation of RCC pts correlates with disease progression. A phase I trial was designed using a xenogeneic murine versus human PSMA DNA vaccine to evaluate safety in pts with RCC. Eighteen pts with clear cell RCC status post nephrectomy, cytokine therapy, or post metastastectomy with high risk of recurrent disease were enrolled. Good risk pts were defined as having a KPS of >80%, prior nephrectomy, normal calcium and hemoglobin levels. Methods: Six pts each were assigned to dose levels (500, 1500 and 3000μg) and were randomized to receive 3 murine or 3 human PSMA DNA vaccines im every 3 weeks. After the third vaccine, pts were crossed-over to the other species for an additional 3 vaccines. If pts remained disease-free or had clinically responding disease, booster immunizations were administered bimonthly for up to 4 additional booster vaccinations at weeks 24, 32, 40 and 48. Results: Ten of 15 treated pts were evaluable. The vaccine was well-tolerated. One pt from the 500μg dose level who received the murine vaccine first, and 2 pts from the 1500μg dose and 1 pt from the 3000μg dose who received the human PSMA DNA vaccine first, remain on study at 167, 114, 125 and 68 weeks, respectively. FACS analysis of pts’ sera against 3T3 fibroblasts genetically transduced to secrete PSMA showed no reactivity at the 500μg dose level; 1 of 2 pts at 1500μg and 1 pt at the 3000μg dose showed reactivity against PSMA, respectively. Minimal activity was seen by ELISA. Conclusions: The vaccine was safe at all dose levels without autoimmunity. The 2 pts at the 1500μg dose level have stable lung lesions. Studies are ongoing to examine other parameters of immune responsiveness. Supported by the Byrne Foundation No significant financial relationships to disclose.