Phase I trial of anti-PSMA designer T cells in advanced prostate cancer.

Abstract

130 Background: We created chimeric immunoglobulin-T cell receptors (IgTCR) specific for prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” (dTc) specifically kill prostate cancer cells in vitro and in vivo in animal models, with 5/9 (55%) of xenografted mice experiencing complete remissions (Ma et al. Prostate 2004:61:12–25). A phase I clinical trial was approved by the FDA. Methods: Patient T cells are retrovirally transduced and expanded ex vivo to span dose levels of 10^9 to 10^11 T cells. Patients undergo prior non-myeloablative (NMA) conditioning to create “hematologic space” into which designer T cells are infused for stable engraftment and prolonged in vivo efficacy. Patients are co-administered continuous infusion IL2. Outcomes include Phase Ia goals of safety and Phase Ib goals of establishing an optimal biologic dose in terms of designer T cell engraftment. Results: Five patients have been treated, three at 10^9 and two at 10^10 cell dose levels. Excellent T cell modifications of 30%-60% were obtained. After NMA conditioning, T cells were infused. Stable engraftments of 1%-20% post-recovery at one month after T cell infusion, thus affirming one of the study end-points. Patients experienced neutropenic fever after conditioning, but no designer T cell-related toxicities. Two patients had partial responses with PSA reductions of 50 and 70% in the two months following treatment with projected benefits of 4 months gain of time to return to starting PSA levels. Results will be updated at the conference. Conclusions: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised with encouraging early results. Patients are being actively recruited. This clinical trial received partial funding from the US Army/DOD. Preclinical work was supported by the Prostate Cancer Foundation. No significant financial relationships to disclose.