Abstract
Abstract Introduction: We created chimeric antigen receptors (CAR) 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 (Ma et al. Prostate 2004:61:12-25). A Phase I clinical trial was approved by the FDA under BB-IND 12084. With the recent publicity surrounding use of this technology to suppress and potentially cure CLL [Porter et al. NEJM 2011:365:725-33], the current aim to apply dTc in metastatic HRPC gains a heightened impetus and significance. Methods: Patient T cells are retrovirally transduced and expanded ex vivo to span the dose range of 10⁁9 to 10⁁11 T cells. Patients undergo prior non-myeloablative (NMA) conditioning to create a “hematologic space” into which dTc are infused for stable engraftment and improved in vivo efficacy. Patients are co-administered continuous infusion IL2. Patients are monitored for safety and response. Outcomes include Phase Ia goals of safety and toxicity and Phase Ib goals of establishing an optimal biologic dose in terms of dTc engraftment and tumor response. Results: To date five subjects have been treated, three at the 10⁁9 cell dose and two at the 10⁁10 cell dose. Excellent T cell modifications of 30-60% were obtained. After NMA conditioning, T cells were infused and stable engraft—ments of 1-20% were observed one-month post recovery, thus affirming one of the study end-points, even at the lowest 10⁁9 dose level, reflecting near 100-fold expansions of dTc in vivo. Two of five patients (40%) had PSA reductions of 50 and 70% in the two months following treatment, whereas four patients (80%) had delays in PSA progression of 2-5 months. Patients experienced neutropenia and lymphopenia after conditioning, but no designer T cell related toxicities. Patient treatments will continue under the dose escalation plan. Conclusion: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised with exciting early results. We postulate that the greater potency of higher dTc doses under adequate IL2 support will induce PSA reductions of 100%, potentially with durable remissions of metastatic prostate cancer that is refractory to all other treatments. Patients are being actively recruited. For referrals, contact by phone: (401) 456-2507 or email: RDavies@rwmc.org. This clinical trial received partial funding from US Army/DOD. Preclinical work was supported by the Prostate Cancer Foundation. Note: This abstract was not presented at the conference because the presenter was unable to attend. Citation Format: Richard P. Junghans, Qiangzhong Ma, Ritesh Rathore, Robin Davies, Anthony Bais, Erica Gomes, Ryan Harvey, Steven I. Cohen. Phase I trial of anti-PSMA designer T cells in advanced prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C13.
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