5127 Background: The purpose of this study was to determine whether immunization with an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant interleukin-2 (IL-2) and interferon-γ (IFN-γ), would be tolerated and able to induce a prolongation of PSA doubling time in patients with progressive hormone refractory prostate cancer. Methods: 30 HLA-A0201-matched patients with progressive, hormone refractory prostate cancer, demonstrating three successive elevations in prostate specific antigen (PSA) values, received four intradermal injections on days 1, 15, 29 and 92, and then every 90 days as long as no tumor progression occurred. Three patients received a dose level of 7.5 million cells, 27 patients received 15 million cells. The primary efficacy criterion was the difference in PSA doubling time (PSA-DT) determined in the pre-treatment phase (before start of vaccination) and in the trial treatment phase (during vaccination). Results: The study was completed according to protocol. Immunostimulation could be demonstrated in most of the 30 patients (histological evaluation of injection site biopsies, serial ELISPOT analysis of PBMCs). During vaccination there was a significant prolongation of the PSA-DT compared to the pre-vaccination period that came to 81% (prolongation from 63 days to 114 days (p < 0.0035; ITT)). Twenty two of 30 patients (73%) responded to the vaccine administration as judged by prolongation of PSA-DT. In the majority of patients the administration was followed by a period of PSA stabilisation that was up to 641 days (“PSA plateau”). No dose limiting or autoimmune toxicities were seen. The median overall survival time since first vaccination was 981 days (mean value: 770 days). Conclusions: This vaccine strategy showed a prolongation of PSA-DT and was found to be safe and well tolerated. The results of this trial warrant the vaccine’s further clinical development. No significant financial relationships to disclose.
Targeting Human γδ T Cells with Zoledronate and Interleukin-2 for Immunotherapy of Hormone-Refractory Prostate Cancer
