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

Abstract

e13614 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” specifically kill prostate cancer cells in vitro and in vivo in animal models (Ma et al. Prostate 2004:61:12-25). A phase I clinical trial was approved by the FDA in metastatic prostate cancers. 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 a “hematologic space” into which the designer T cells are infused to expand and stably engraft for prolonged in vivo efficacy. Patients are co-administered continuous infusion outpatient IL2 at 75,000 IU/kg/d ×28d. Outcomes include phase Ia goals of safety and toxicity and phase Ib goals of establishing an optimal biologic dose in terms of designer T cell engraftment and tumor response. Results: Three patients were treated at the 10^9 cell dose and one at the 10^10 cell dose. All patients experienced neutropenia and fever post conditioning, but no designer T cell-related toxicities. T cells were infused and engraftments of 1-20% were observed one-month post recovery, thus affirming one of the study end-points. Two patients (both at the 10^9 cell level) had PSA reductions of 50 and 70% in the two months following treatment, whereas two had no response (<20%) (one at 10^9 and one at 10^10 cells). Systemic IL2 was more than 10-fold lower in the two non-responders than in the two responders (2 IU/ml versus 30 IU/ml), suggesting need for adequate IL2 to realize designer T cell therapeutic activity. Patient enrollments are ongoing; data will be updated at conference time. 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. No significant financial relationships to disclose.