Car body design summary
Finally, simplified methods to culture and engineer T cells are required to lower the costs, accelerate development, and improve access to this novel treatment. 21, 22 However, with rare exceptions, clinical responses in patients with solid tumors have been minor and transient, highlighting the importance of optimizing T cell therapeutics to tackle the solid tumor challenge. Moreover, evidence of transient antitumor activity has been observed in patients with difficult-to-treat tumors. 17, 18, 19, 20 We define engraftment as the ability for CAR T cells to be detectable in peripheral blood at any time after infusion. Recent clinical reports suggest that CAR T cells can engraft in the peripheral blood, traffic to solid tumors, and respond to antigen. 3, 10, 16 Fourth, in order to be effective in solid tumors, CAR T cells will have to overcome multiple challenges, including an immunosuppressive tumor microenvironment. Third, although finding a single uniquely expressed tumor antigen is already a challenge, 15 targeting only one antigen may be insufficient to obtain sustained responses, because antigen loss has been identified as a frequent cause of tumor resistance to CAR T cell therapies. 12 Second, active proliferation of the CAR T cells in the body can itself lead to potentially serious side effects, such as cytokine release syndrome 13 and neurologic toxicity, 14 although these are typically transient and reversible. First, the potency of these “living drugs” can lead to lethal on-target toxicity if the target is expressed on a life-sustaining tissue. 10, 11Īlthough the human T cell is a highly potent anti-tumor agent, several challenges remain for successfully applying CAR T cells to solid tumors. Emerging clinical data are proving the potential of CD22 and B cell maturation antigen (BCMA)-directed CAR T cells to eradicate leukemia and multiple myeloma, respectively, heralding a new era for the treatment of blood cancers. 3, 4, 5, 6, 7, 8, 9 CAR T cells targeting CD19 were recently approved by the US Food and Drug Administration (FDA) and the European Commission (EC) for the treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in pediatric and young adults (Kymriah), and for the treatment of relapsed or refractory diffuse large B cell lymphoma in adults (Kymriah and Yescarta). 1 Together with checkpoint blockade therapy, 2 CAR T cells are revolutionizing the field of cancer therapies, providing hope to patients with previously refractory cancers. Adoptive transfer of T cells collected from autologous peripheral blood and engineered to express chimeric antigen receptors (CARs) has produced impressive clinical responses in patients with hematologic malignancies.