Dr Brentjens conducted initial pre-clinical studies demonstrating the potential clinical application of autologous T cells genetically modified to target the CD19 antigen through the retroviral gene transfer of artificial T cell receptors termed chimeric antigen receptors (CARs) during his Medical…
more Oncology fellowship training under the mentorship of Dr Michel Sadelain. Subsequently, as a PI, Dr Brentjens successfully translated these studies to the clinical setting treating patients with relapsed CD19+ tumors including chronic lymphocytic leukemia (CLL), B cell acute lymphoblastic leukemia (B-ALL), and high risk diffuse large B cell lymphomas (DLBCL). Initial outcomes from these studies have demonstrated remarkable clinical outcomes particularly in the setting of poor prognosis adult relapsed B-ALL patients. This proof of principle has led to the expansion of clinical enrollment on these studies. Addressing potential limitations of this therapeutic approach, additional pre-clinical research in the laboratory is focused on the further development of CAR modified T cells designed to overcome the hostile immunosuppressive tumor microenvironment through the generation of “armored CAR T cells” designed to secrete proinflammatory cytokines (IL-12) as well as costimulatory ligands (CD40L). These next generation CAR T cells are currently being translated to the clinical setting. Additionally, work in the Brentjens’ lab has expanded this CAR technology to target additional tumor antigens expressed on other tumors including targeting CD33 on acute myelogenous leukemias (AML), the MUC-16 antigen expressed on ovarian carcinomas, as well as the more ubiquitous WT-1 tumor associated antigen. These latter projects are similarly in the process of translation to the clinical setting.
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