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. Author manuscript; available in PMC: 2022 Mar 7.
Published in final edited form as: Cell. 2020 Apr 2;181(1):46–62. doi: 10.1016/j.cell.2020.03.001

Figure 3. Engineering strategies to enhance adoptive Immune cell therapy.

Figure 3.

Sophisticated bioengineering approaches are under development to enhance the potency, specificity, and safety of T cell therapies. Suicide switches, AND gating, and adaptor CAR platforms are being developed to mitigate CAR-mediated toxicity. Ectopic expression of c-Jun or genetic deletion of NR4a factors endows CAR T cells with exhaustion resistance, potentially improving efficacy in solid tumors and enhancing persistence. CAR T cells can also be engineered to secrete specific factors to augment expansion or persistence (e.g., IL-7, IL-12, IL-15, or IL-21), diminish the need for a lymphodepleting regimen, resist the suppressive tumor microenvironment (e.g., secretion of IL-18, expression of a truncated transforming growth factor β [TGF-β] receptor), or act as tumor-specific drug delivery vehicles (e.g., local secretion of anti-PD-1).