Abstract IA16: Engineered T cell therapies for cancer.

Abstract

Abstract Chimeric antigen receptors (CARs) combine an antigen recognition domain of a specific antibody with a intracellular signaling domains into a single engineered protein. CD19 is an ideal target for CARs since expression is restricted to normal and malignant B cells. In preclinical studies, inclusion of the CD137 (4-1BB) signaling domain results in remarkable antitumor activity and in vivo persistence of anti-CD19 CARs. We have previously reported dramatic in-vivo expansion, persistence and anti-tumor activity of CAR modified autologous T cells targeted to CD19 (CART19 cells) in 3 patients with CLL with relatively short follow up (Porter, et al NEJM 2011; Kalos et al Sci Trans Med 2011). Currently, 11 patients have been treated with CART19 cells. There were 9 adults (median age 65 years (range 51-78)) treated for relapsed, refractory and high risk CLL and two pediatric cases treated for relapsed refractory pre-B cell ALL. CLL patients had received a median of 5 prior regimens excluding single agent rituxumab (range 2-10) and all had active disease at the time of cell infusion. The pediatric patients with ALL had chemotherapy refractory relapse, and one was resistant to allogeneic transplantation and CD19 directed blinotumomab. A median of 7.5 x 10^8 total cells (range 1.7-50) corresponding to 1.45 (range 0.14-5.9 x 108) genetically modified cells were infused. In the patients in complete remission, CAR modified CART19 cells are detectable in the peripheral blood by flow cytometry at the most recent follow up for at least 2 years. All patients in CR have B cell aplasia. No patient with CR has progressed. Citation Format: Carl H. June. Engineered T cell therapies for cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA16.