Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen

Abstract

BACKGROUND: Conventional treatment for metastatic prostate cancer have failed to demonstrate curative potential in all patients. Investigations involving the role of T-cell immunity in the clearance of neoplastic cells are now available. Development of T-cell immunotherapy may give a new approach to the treatment of advanced metastatic prostate cancer. METHODS: A phase I clinical trial assessing the administration of autologous dendritic cells (DC) pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides were conducted. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (groups 4 and 5, respectively). RESULTS: No significant toxicity was observed in all five groups. Cellular response against PSM-P1 and -P2 was observed in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (groups 4 and 5), respectively. An average decrease in PSA was detected only in group 5. Seven partial responders were identified based on NPCP criteria + PSA. CONCLUSIONS: Infusions of test substances were well tolerated by all study participants. Detection of cellular response and decrease in PSA level in some patients who received DC pulsed with PSM-P2 indicate this method's potential in prostate cancer therapy.