So we designed CAR-T cells to produce IL-2 using synNotch. Now, when a CAR-T cell encounters a tumor, it produces IL-2 within the tumor instead of outside it, avoiding causing harm to surrounding healthy cells. Because synNotch is able to bypass the barriers tumors put up, it is able to help T cells amp up and maintain the amount of IL-2 they can make, allowing the T cells to keep functioning even in a hostile microenvironment.
We tested our CAR-T cells modified with synNotch on mice with pancreatic cancer and melanoma. We found that CAR-T cells with synNotch-induced IL-2 were able to produce enough extra IL-2 to overcome the tumors’ defensive barriers and fully activate, completely eliminating the tumors. While all of the mice receiving synNotch modified CAR-T cells survived, none of the CAR-T-only mice did.
Furthermore, our synNotch modified CAR-T cells were able to trigger IL-2 production without causing toxicity to healthy cells in the rest of the body. This suggests that our method of engineering T cells to produce this toxic cytokine only where it is needed can help improve the effectiveness of CAR-T cells against cancer while reducing side effects.
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