Abstract IA17: Adoptive T cell therapy with CAR modified T cells: We have a Model A Ford, can we build a Ferrari?

Abstract

Abstract Recently published reports support the novel approach of treating cancer with patient derived T cells genetically modified to express artificial T cell receptors, termed chimeric antigen receptors (CARs), targeted to tumor associated antigens. To this end, initial clinical trial outcomes of patients with relapsed B cell acute lymphoblastic leukemia (B-ALL) treated with T cells genetically modified to express a CAR specific to the CD19 antigen demonstrate that this approach is a very promising therapeutic intervention which potentially may dramatically alter the standard of care in this disease. In contrast far more modest clinical responses were seen in patients with relapsed low grade B cell malignancies including chronic lymphocytic leukemia (CLL) and B cell non-Hodgkins lymphomas (NHL). The etiologies of discordant clinical outcomes between B-ALL and CLL/NHL patients treated with CD19 targeted CAR T cells remains a subject of conjecture although the tumor microenvironment is a strong focus for further investigation. To this end, we will present novel data on a next generation of CAR T cells, termed “armored CAR” T cells genetically designed to enhance persistence, anti-tumor efficacy, and an ability to overcome an immune suppressive tumor microenvironment through further genetic modification. Promising preclinical studies utilizing various “armored CAR” T cell approaches and their role in future clinical trials will be discussed as well as the relevance of these findings to the extrapolation of this technology from hematologic tumors to far more prevalent solid tumor malignancies. Note: This abstract was presented as part of the Joint Session: Clinical Science Interactions between Melanoma and Hematologic Malignancies with the AACR Special Conference on Advances in Melanoma: From Biology to Therapy held September 20-23, 2014 in Philadelphia, PA. Citation Format: Renier Brentjens. Adoptive T cell therapy with CAR modified T cells: We have a Model A Ford, can we build a Ferrari? [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA17.