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Designer protein circuits enable safe cancer immunotherapy
Synthetic receptor proteins can enable customized and flexible control of immune cells called T lymphocytes. A defined framework for the proteins’ design now improves their potential for use in cancer immunotherapy.
Mohamad Hamieh is at the Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA, and at the Immunology Program, Sloan Kettering Institute, New York.
Maria Themeli is in the Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands, and at the Cancer Center Amsterdam.
A promising tool in the fight against cancer is CAR T therapy, in which immune cells called T cells are engineered to express a synthetic receptor protein, the chimeric antigen receptor (CAR), on their surface. CAR proteins recognize an extracellular target — an antigen molecule from a nearby tumour cell — and stimulate the T cell to trigger an immune cascade in response. However, the widespread application of this emerging therapy in tumours is limited by the lack of truly tumour-specific antigens, which often leads to unwanted side effects in healthy tissues. The design of synthetic-protein circuits that prevent CAR T cells from being activated outside tumours could reconcile potency with safety. Writing in Cell, Zhu et al.1 describe one such system of proteins.