Abstract 1540: Allogeneic chimeric antigen receptor T cells targeting B cell maturation antigen

Abstract

Abstract B cell maturation antigen (BCMA) is a tumor necrosis factor family cell surface receptor that binds B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) and is involved in the long-term survival of B cells. BCMA has been shown to be expressed broadly on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) cells and for this reason has been pursued as a potential antigen for the treatment of MM. Indeed, clinical studies evaluating autologous chimeric antigen receptor T cells (CAR-T cells) targeting BCMA for the treatment of MM have shown promising efficacy with >80% response rates. However, logistical challenges will potentially limit the number of patients that have access to autologous therapies. Using the CRISPR/CAS9 system, we generated allogeneic CAR-T cells targeting BCMA by disrupting the beta-2-microglobulin (B2M) and T cell receptor alpha constant (TRAC) genes and inserting an anti-BCMA CAR into the TRAC locus. This results in allogeneic CAR-T cells lacking the major histocompatibility complex (MHC) and endogenous T cell receptor (TCR) expression while being potently cytotoxic towards cells expressing BCMA. These data show proof-of-concept for an “off the shelf” CAR-T therapy targeting BCMA. Citation Format: Henia Dar, Daniel Henderson, Zinkal Padalia, Ashley Porras, Dakai Mu, Kyungah Maeng, Seshi Police, Demetrios Kalaitzidis, Jonathan Terrett, Jason Sagert. Allogeneic chimeric antigen receptor T cells targeting B cell maturation antigen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1540.