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

BACKGROUND. Conventional treatment for metastatic prostate cancer have failed to demonstrate curative potential in all patients. Investigati ons involving the role of T-cell, immunity in the clearance of neoplas tic cells are now available. Development of T-cell immunotherapy may g ive a new approach to the treatment of advanced metastatic prostate ca ncer. METHODS. A phase I clinical trial assessing the administration o f autologous dendritic cells (DC) pulsed with HLA-A0201-specific prost ate-specific membrane antigen (PSMA) peptides were conducted. Particip ants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; groups 1 and 2, respectively), auto logous DC (group 3), or DC pulsed with PSM-P1 or P2 (groups 4 and 5, r espectively). RESULTS. No significant toxicity was observed in all fiv e 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 an d 5), respectively. An average decrease in PSA was detected only in gr oup 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 indi cate this method's potential in prostate cancer therapy. (C) 1996 Wile y-Liss, Inc.