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Background: There is presently no effective therapy for relapsing, metastatic, androgen-independent prostate cancer. Immunotherapy with monoclonal antibody-vehicled toxins (Immunotoxins, ITs) may be a promising novel treatment option for the management of prostate cancer in these cases., Methods: Three anti-prostate specific membrane antigen (anti-PSMA) monoclonals (J591, PEQ226.5, and PM2P079.1) were cross-linked to ricin A-chain (RTA; native or recombinant), and their cytotoxic effects were investigated in monolayer and three-dimensional (3-D) cell cultures of prostate carcinoma cells (LNCaP)., Results: The various Immunotoxins showed effects in the nanomolar range (IC(50s) of 1.6-99 ng/ml) against PSMA+ cells (IC(50) being the concentration inhibiting 50% cell proliferation or protein synthesis). PSMA(-) cell lines were 62- to 277-fold less sensitive to anti-PSMA ITs, evidencing an appreciable therapeutic window. Treatment with J591-smpt-nRTA (0.35-31.7ng/ml) resulted in complete eradication of 3-D tumor micromasses or in 1.46- to 0.35-log reduction of target cells number, depending on the dose., Conclusion: Anti-PSMA ITs appear to be promising for use in the eradication of small prostate tumor cell aggregates present in tissues and in the bone marrow., (Copyright 2002 Wiley-Liss, Inc.)

Background: A phase II trial, involving infusions of autologous dendritic cells (DC) and two human histocompatibility antigen (HLA-A2)-specific prostate-specific membrane antigen (PSMA) peptides, was recently completed. Thirty percent of the participants, including subjects with hormone-refractory metastastic disease, and those with suspected local recurrence of prostate cancer, were identified as clinical responders. This report describes the follow-up evaluation of 19 responders in the two study groups., Methods: After conclusion of the study, study participants were subjected to follow-up evaluations at 6-8-week intervals. Each responder was reevaluated for response status, and duration of response was determined., Results: Subjects were observed for an average of 291 days (metastastic group, group A-2) and 557 days (local recurrence group, group B), which included the treatment and follow-up periods. The average duration of response was 149 days for group A-2, and 187 days for group B. A majority of responders (11/19; 58%) were still responsive at the end of the current follow-up., Conclusions: The responses observed may be significant and relatively durable. This study suggests that DC-based cancer vaccines in the future may provide an additional therapy for advanced prostate cancer.

Background: In this paper we describe our program for the immune monitoring of phase II participants given dendritic cell (DC)/prostate-specific membrane antigen (PSMA)-based immunotherapy, and we also present some initial findings., Methods: Phase II subjects received six administrations of autologous dendritic cells exogenously pulsed with two peptides derived from PSMA. Prior to the initial infusion, and following each treatment, peripheral blood mononuclear cells (PBMC) were collected for the generation of dendritic cells as well as for comprehensive immune monitoring., Results: Thus far, an increase in PSMA-peptide-specific as well as overall cellular reactivity has been observed in several patients receiving DC plus PSM-P1 and -P2, as measured by delayed-type 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 cancer patients following infusion with DC plus PSMA-derived peptides. Several methods are underway to comprehensively monitor both cell-mediated and humoral immune responsiveness, including: determining anti-PSMA serum antibody titers, testing immunogen-restricted responder-cell proliferation and cytotoxicity, assessing aberrations in signal transduction, antigen processing, and presentation, and measuring soluble factors that may promote tumor outgrowth.