Abstract
The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. The development of strategies for flexible and modular CAR T systems is accelerating, allowing for multiple antigen targeting, precise programming, and adaptable solutions in the field of cellular immunotherapy. Moving beyond the fixed antigen specificity of traditional CAR T systems, the modular CAR T technology splits the T cell signaling domains and the targeting elements through use of a switch molecule. The activity of CAR T cells depends on the presence of the switch, offering dose-titratable response and precise control over CAR T cells. In this review, we summarize developments in universal or modular CAR T strategies that expand on current CAR T systems and open the door for more customizable T cell activity.
Highlights
Engineering T cells to express chimeric antigen receptors (CARs) has shown wide-ranging potential as a potent anti-cancer therapeutic
We summarize emerging systems developed to overcome the limitations of CARs with fixed antigen specificity using universal CAR T strategies
In an effort to target this reservoir of HIV-infected cells, the authors employed convertibleCAR T cells armed with anti-HIV antibodies fused to an orthogonal MIC ligand
Summary
Engineering T cells to express chimeric antigen receptors (CARs) has shown wide-ranging potential as a potent anti-cancer therapeutic. Numerous studies showed high remission rates, rapid tumor eradication, and durable responses in patients with refractory disease, raising expectations for expanding the types of cancers that can be treated with CAR therapy [3,4,5] These results are encouraging, several challenges exist that inhibit the broad application of this treatment. Modular CAR T cells are not targeted at the tumor antigen itself; instead, the CAR is directed at at anan adaptor or or switch element This adaptor serves asas thethe targeting element, is directed adaptor switch element.
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