Building a CAR Garage: Preparing for the Delivery of Commercial CAR T Cell Products at Memorial Sloan Kettering Cancer Center

Abstract

Two commercial chimeric antigen receptor (CAR) T cell therapies for CD19-expressing B cell malignancies, Kymriah and Yescarta, have recently been approved by the Food and Drug Administration. The administration of CAR T cells is a complex endeavor involving cell manufacture, tracking and shipping of apheresis products, and management of novel and severe toxicities. At Memorial Sloan Kettering Cancer Center, we have identified 8 essential tasks that define the CAR T cell workflow. In this review, we discuss practical aspects of CAR T cell program development, including clinical, administrative, and regulatory challenges for successful implementation.

Keywords: Acute lymphoblastic leukemia; CAR T cells; Cellular therapy; Chimeric antigen receptor; Cytokine release syndrome; Diffuse large B cell lymphoma.

Figure 1:. Antigen Recognition by T cells

T cell receptors recognize intracellular antigens presented as peptides in the context of major histocompatibility complex (MHC). First generation (1G) CAR T cells target extracellular tumor-associated antigens using an antibody-derived Single Chain Variable Fragment (scFV; blue) fused to an adaptor domain (tan) and internal CD3ζ signaling domain (purple). Second Generation (2G) CAR T cells incorporate a co-stimulatory domain (red) for enhanced T cell function. Co-stimulation is commonly provided through signaling of CD28 or 4-1BB.

Figure 2:

The eight essential steps required to establish a CAR T cell program and the personnel required to implement them. Key regulatory agencies involved in each step are denoted by a bullet.