Health
Using synthetic genetic circuits to better control the timing of immunotherapy
In two separate studies, researchers show how synthetic biology can be used to tackle the difficult problem of cancer immunotherapy. Immunotherapy-related approaches that focus on short-term killing of tumor cells may fail to eradicate tumors because tumor growth occurs over a longer timescale. Here, two research groups use synthetic genetic circuits that can activate anti-tumor cell function only on demand or in the case of CAR, so that the timing of immunotherapy can be better controlled. We present a strategy to T cells in direct contact with tumor cells. Emmanuel Salazar-Cavazos and Grégoire-Altin-Bonnet wrote, “Rather than being limited by ‘natural’ immunology (using leukocytes, antibodies, and cytokines), these studies are directed to CAR T against diseased tissue.” It expands the range of immune responses elicited by cells.” A relevant perspective.
Among cancer immunotherapy arsenals, chimeras antigen Receptor (CAR) T therapies include ex vivo A patient’s cancer-killing T cells are engineered to express CARs that recognize specific molecules on the tumor surface. These are injected into patients to induce an immune response against cancer cells. However, CAR T-cell therapies are usually optimized for short-term cellular responses (eg, tumor cell killing) and may not achieve long-term systemic tumor eradication. To enable precise control of CAR T cell function over time, Greg Allen and colleagues took advantage of the recently developed synthetic Notch receptor to Engineering enhanced CAR T cells with a second receptor. A second receptor can recognize tumor antigens and subsequently cause her T cells to release the cytokine interleukin-2, which only occurs when her CAR T cells are in direct contact with tumor cells. Limited. In a mouse model, the approach resulted in CAR T infiltration into the solid pancreas, melanoma Resulting in virtual eradication of tumors. Importantly, these tumor-targeted IL-2 delivery circuits offer a potential way to locally target tumors while minimizing IL-2’s long-standing toxicity problems, the authors say. said.
In their study, Hui-Shan Li and colleagues developed a toolkit of 11 programmable synthetic transcription factors that can be activated on demand by timed administration of FDA-approved small-molecule inducers. . Using these tools, the authors engineered human immune cells that activate specific cellular programs (such as proliferation and anti-tumor activity) on demand. This allows for a graded and time-controlled therapeutic response. “A combination of two technological advances presented by Li and others. and Allen and others. Salazar-Cavazos and Altan-Bonnet enable unprecedented ability to precisely control the state of therapeutic cell populations “not only at the time of injection, but also while the immune response is developing in the patient’s body.” .
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Journal reference:
Allen, GM, and others. (2022) A synthetic cytokine circuit that directs T cells to immune-excluded tumors. Chemistry. doi.org/10.1126/science.aba1624.
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