In two separate studies, researchers demonstrate how synthetic biology can be used to tackle a difficult issue in cancer immunotherapy: the way immunotherapy-related approaches focused on short-term killing of tumor cells may fail to eradicate tumors because growth of tumors happens on longer timescales. Here, two research groups present strategies to allow better control over the timing of immunotherapy using synthetic gene circuits whereby anti-tumor cell functions can be activated on demand, or only when CAR (chimeric antigen receptor) T cells are in direct contact with tumor cells. “Rather than being limited by ‘natural’ immunology (using leukocytes, antibodies, and cytokines), these studies expand the scope of immune responses elicited by CAR T cells against disease tissues,” write Emmanuel Salazar-Cavazos and Grégoire Altan-Bonnet in a related Perspective. The research articles are titled “Synthetic Cytokine Circuits That Drive T Cells into Immune-Excluded Tumors,” by Greg Allen et al. at UCSF and “Multidimensional Control of Therapeutic Human Cell Function with Synthetic Gene Circuits,” by Hui-Shan Li et al. at Boston University. The Perspective is titled “Engineering Time-Controlled Immunotherapy.” The publications appeared in Science on December 15-16, 2022.
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