Bispecific Chimeric Antigen Receptor T Cell Therapy for B Cell Malignancies and Multiple Myeloma

Abstract

Chimeric antigen receptor (CAR) modified T cell therapy offers a targeted immunotherapeutic approach to patients with refractory hematological malignancies. This technology is most advanced in B cell malignancies and multiple myeloma and is rapidly evolving as more data become available regarding clinical efficacy and response durability. Despite excellent initial response rates with single antigen targeting CARs, failure to respond to therapy and relapse due to target antigen downregulation remain clinical challenges. To mitigate immunophenotypic selective pressures, simultaneous dual antigen targeting with bispecific CAR T cells or multiple administration of different populations of CAR T cells may prevent relapse by addressing one resistance mechanism attributed to antigenic loss. This article will review recently published data on the use of dual targeting with CAR T cells from early phase clinical trials aimed at treating B cell malignancies and multiple myeloma.

Keywords: ALL; BCMA; CAR T cell; CD19; CD20; CD22; CD38; NHL; bispecific; myeloma.

Figure 1

Dual antigen chimeric antigen receptor CAR T approaches. (a) Coadministration: involves production of two separate CAR T cell products infused together or sequentially. (b) Bicistronic: allows expression of two different CARs on the same cell. (c) Cotransduction: encodes two CAR constructs with multiple vectors. With this process, one will also obtain cells that express each CAR alone. (d) Tandem: encodes two CARs on same chimeric protein using a single vector. This work is licensed under a CC-BY Creative Commons attribution license, version 4.0 [32].