Follow‐up evaluation of a phase II prostate cancer vaccine trial

Abstract

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.

Induction of autoantibodies to syngeneic prostate‐specific membrane antigen by xenogeneic vaccination

“…In one PhaseI/II trial, patients with advanced disease were immunized with PSMA peptides pulsed onto autologous antigen presenting cells, 21,22 and minor T cell reactivity was observed. Other patients immunized with naked PSMA DNA vaccines alone or in combination with adenovirus encoding PSMA 20,39 developed DTH responses to PSMA, while immune sera showed no reactivity to PSMA protein when tested by Western blot.…”

“…[12][13][14][15][16][17][18] The safety profile of passive immunotherapy with J591 and its derivatives, along with specific localization of radionuclide-labeled MAb to tumor sites in patients with metastatic prostate cancer or other solid tumors, supports the potential clinical benefit of antibodies and T cells specific for PSMA induced by active immunization. In addition to these studies, clinical trials of active immunotherapy have been completed with no evidence of toxicity, [19][20][21][22] and some anecdotal declines in serum prostate-serum antigen (PSA) were reported.…”

Comparison of Anti‐Tumor Responses against TL Positive Lymphoma Induced by Skin Grafting and Dendritic Cell Immunization

“…4 Many reports on DC-based vaccine models have appeared in journals in the last few years (23,30,38,39,42), but one concern is that investigators tend to study tumor models with immunogenicity too strong to be comparable to the naturally occurring tumor antigens. Basic studies with a weak antigen model such as TL, however, may provide valuable information for immunotherapy of cancer patients.…”

Immunology and immunotherapy approaches for prostate cancer

“…Murphy and Tjoa [160][161][162][163][164] have performed several phase I and II clinical trials of the use of PSMA-derived peptide-pulsed DC for patients with locally advanced or metastatic PC. They loaded monocyte-derived DC with one of two HLA-A2-restricted PSMA-derived peptides (PSM-P1 and PSM-P2), and administered them intravenously.…”