Abstract IA20: Moving CAR T cell therapy forward: CARs and armored CARs

Abstract

Abstract T cells may be genetically modified to express chimeric antigen receptors (CAR) targeted to antigens expressed by tumor cells. We have developed this technology in the laboratory and translated this adoptive T cell approach in the clinic. Treatment of patients with CD19 targeted CAR T cells has resulted remarkable remission rates in relapsed B cell acute lymphoblastic leukemia (B-ALL). Specifically, based on currently updated clinical outcomes, we have achieved >85% CR rates in adult patients with relapsed B-ALL treated with CD19 targeted CAR T cells which far exceed historical expectations. Further, by deep sequencing analysis, most treated patients were MRD- after CAR T cell therapy. Significantly, remissions were observed in both patients with overt morphological residual disease at the time of therapy as well as in patients with only residual MRD+ disease. Clinical trials form other centers which confirm the presented clinical trial outcomes from our center will be reviewed. While overall generally well tolerated, we found that patients treated with CAR T cells in the setting of overt disease experienced a cytokine release syndrome (CRS) with associated fevers, hypotension, and mental status changes including overt seizures. In contrast, far more modest responses were seen in patients with relapsed chronic lymphocytic leukemia (CLL). The discordant clinical outcomes between B-ALL and CLL patients treated with CD19 targeted CAR T cells remains a subject of conjecture although the tumor microenvironment is a strong focus of further investigation. To this end, we will present novel data on a next generation of CAR T cells, termed “armored CARs” further genetically designed to overcome an immune suppressive tumor microenvironment through further genetic modification of CAR T cells. Promising preclinical studies utilizing these “armored CAR” T cell approaches and their role in future clinical trials will be discussed. Citation Format: Renier J. Brentjens. Moving CAR T cell therapy forward: CARs and armored CARs. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA20.