REPORT OF IMMUNE MONITORING OF PROSTATE-CANCER PATIENTS UNDERGOING T-CELL THERAPY USING DENDRITIC CELLS PULSED WITH HLA-A2-SPECIFIC PEPTIDES FROM PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)

BACKGROUND. In this paper we describe our program for the immune monit oring of phase II participants given dendritic cell (DC)/prostate-spec ific membrane antigen (PSMA)-based immunotherapy, and we also present some initial findings. METHODS. Phase II subjects received six adminis trations of autologous dendritic cells exogenously pulsed with two pep tides derived from PSMA. Prior to the initial infusion, and following each treatment, peripheral blood mononuclear cells (PBMC) were collect ed for the generation of dendritic cells as well as for comprehensive immune monitoring. RESULTS. Thus far, an increase in PSMA-peptide-spec ific as well as overall cellular reactivity has been observed in sever al patients receiving DC plus PSM-P1 and -P2, as measured by delayed-t ype hypersensitivity (DTH) test and enzyme-linked immunosorbant assay (ELISA). CONCLUSIONS. Our initial observations using an ELISA and DTH test indicate that we are enhancing cellular immunity in prostate canc er patients following infusion with DC plus PSMA-derived peptides. Sev eral methods are underway to comprehensively monitor both cell-mediate d and humoral immune responsiveness, including: determining anti-PSMA serum antibody titers, testing immunogen-restricted responder-cell pro liferation and cytotoxicity, assessing aberrations in signal transduct ion, antigen processing, and presentation, and measuring soluble facto rs that may promote tumor outgrowth. (C) 1998 Wiley-Liss, Inc.