Chimeric antigen receptor

Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins, such as surface proteins on cancer cells, that is added to immune cells for immunotherapy strategies such as directing T cells to fight cancer.

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Meredith Hanel
Meredith Hanel edited on 28 Feb, 2019
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Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins on cancer cells that is added to immune cells, for immunotherapy strategies such as T cells.directing T cells modified with a chimeric antigen receptor (CAR), called CAR-T cells, are designed to find and killfight cancer cells that carry the protein recognized by the receptor.

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CARs are recombinant protein molecules that cause cell activation upon encountering the target antigen. The antigen-recognition domain of a CAR is usually derived from monoclonal antibody sequences.Cell therapies being used or in development for treating cancer or autoimmune diseases use T cells or regulatory T cells (Tregs) respectively. CAR-T cells are engineered T cells and CAR-Treg cells are engineered Tregs.

ChimericT cells modified with a chimeric antigen receptorsreceptor (CARsCAR), called CAR-T cells, are recombinantdesigned to find and kill cancer cells that carry the protein molecules that cause cell activation uponrecognized encounteringby the target antigen. The antigen-recognition domain of a CAR is usually derived from monoclonal antibody sequencesreceptor. This region interacts with tumor cell surface proteins and signaling motifs in the intracellular portion of the CAR ensure cell activation. The interaction occurs in a major histocompatibility complex (MHC)-unrestricted manner.This means the interaction does not require MHC compatibility between effector and target cell. This is important because tumors often lose MHC expression as a mechanism of evading detection by endogenous T cells.

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Synthetic Biology Approaches

Improved tumor recognition and specificity has been shown by incorporating the synNotch transcriptional receptor which creates a two antigen tumor recognition circuit. One antigen binds synNotch and primes CAR expression and a second antigen binds CAR to activate the T cell. This system is being used by Cell Design Labs to develop CAR-T therapies.

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