Gerald M. Kenny

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

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.

Infusion of dendritic cells pulsed with HLA‐A2‐specific prostate‐specific membrane antigen peptides: A phase II prostate cancer vaccine trial involving patients with hormone‐refractory metastatic disease

A phase II trial was conducted to assess the efficacy of infusions of dendritic cells (DC) and two HLA‐A2‐specific PSMA peptides (PSM‐P1 and ‐P2). This report describes thirty three subjects with hormone‐refractory metastatic prostate cancer without prior vaccine therapy history who were evaluated and reported as a group.

Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides.

A phase I trial involving patients with advanced prostate cancer was conducted to assess the safe administration of dendritic cells (DC) and HLA‐A0201‐specific prostate‐specific membrane antigen (PSMA) peptides (PSM‐P1 or ‐P2). Thirty‐three of the phase I participants were subsequently enrolled in a phase II trial, which involved six infusions of DC pulsed with PSM‐P1 and ‐P2 peptides.

Phase II Prostate cancer vaccine trial : Report of a study involving 37 patients with disease recurrence following primary treatment

A phase II trial was conducted to assess the efficacy of infusions of dendritic cells (DC) and two HLA‐A2‐specific prostate‐specific membrane antigen (PSMA) peptides (PSM‐P1 and ‐P2). This report describes the evaluation of 37 subjects admitted with presumed local recurrence of prostate cancer after primary treatment failure.

Follow-up evaluation of a phase II prostate cancer vaccine trial.

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.

Presentation of prostate tumor antigens by dendritic cells stimulates T-cell proliferation and cytotoxicity.

Dendritic cells (DCs) are “professional” antigen‐presenting cells capable of stimulating T‐cell proliferation and cytotoxicity when loaded with and presenting specific antigens, including tumor antigens. We demonstrated the stimulation of an autologous cytotoxic T‐cell response elicited by DC loaded with autologous tumor cell lysate derived from primary prostate tumor. A candidate tumor antigen is prostate‐specific membrane antigen (PSMA), which is overexpressed in prostate cancer patients. We identified a HLA‐A2 motif in PSMA, isolated patient DC, loaded peptide into DC, and stimulated autologous T cells to proliferate. The ability to use DC for presentation of either tumor or peptide antigen in an HLA‐restricted fashion in order to stimulate T‐cell proliferation and cytotoxicity demonstrates the potential of this technology for development of a prostate cancer vaccine.

Follow-up evaluation of prostate cancer patients infused with autologous dendritic cells pulsed with PSMA peptides

We recently conducted a phase I clinical trial administering autologous dendritic cells pulsed with prostate‐specific membrane antigen (PSMA) peptides to advanced prostate cancer patients. Participants were divided into 5 groups receiving 4 or 5 infusions of peptides alone (PSM‐P1 or ‐P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM‐P1 or ‐P2 (groups 4 and 5, respectively). Seven partial responders were observed. Follow‐up evaluation of these responders is presented in this report.

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)

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.

Brachytherapy for clinically localized prostate cancer: results at 7- and 8-year follow-up.

In recent years, there has been a resurgence of interest in interstitial radiation as a cost-effective and efficient method of treating organ-confined prostate cancer. We describe our 7- and 8-year results with transperineal Iodine-125 and Palladium-103 implantation. A total of 551 consecutive patients were treated. Of these, 320/551 (58%) received implant alone (Group I), and 231/551 (42%)--considered higher risk patients--were also treated with a modest dose (45 Gy) of external beam irradiation (Group II). The median follow-up for Group I was 55 months, and for Group II, 60 months. At 7 years, the actuarial freedom from biochemical failure (prostate-specific antigen (PSA) < or = 1.0 ng/mL) was 80% in Group I patients, and, at 8 years, 65% in Group II patients. Morbidity was minimal if patients had not undergone prior transurethral prostate resections. The results indicate that interstitial radiation is a valid treatment for clinically localized prostate cancer.

Higher‐dose and less frequent dendritic cell infusions with PSMA peptides in hormone‐refractory metastatic prostate cancer patients

Infusion of dendritic cells (DCs) pulsed with PSMA peptides was considered possible in hormone‐refractory metastatic prostate cancer patients both with or without prior treatment with a greater number of DCs and for lesser infusions than previously administered.