What is the structure of chimeric antigen receptor (CAR) T-cells?

Updated: Dec 17, 2020
  • Author: Sameh Gaballa, MD, MS; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Answer

Chimeric antigen receptors (CARs) are synthetic proteins expressed on the surface of T cells. These receptors have both extracellular and intracellular components. The extracellular component is an antigen-recognizing domain composed of fragments of monoclonal antibodies; it recognizes a specific protein on the surface of malignant cells (eg, CD19 on B-cells). The intracellular domains ensure intracellular signaling necessary to activate the effector functions of the CAR T cell. First-generation CAR T cells utilized an intracellular domain from the CD3 ζ-chain of the T-cell receptor (TCR), which induced cytotoxicity against targeted malignant cells but failed to support CAR T cell expansion in vivo after reinfusion.

In contrast, second- and third-generation CAR T cells have an additional costimulatory intracellular domain (eg, CD28, 41BB, OX40) that enhances the CAR T cells’ ability to proliferate, expand, and persist in vivoEstablishing a favorable cytokine environment within the patient through lymphocyte depletion (commonly accomplished with fludarabine and cyclophosphamide) further enhances the ability of CAR T cells to expand in vivo. [2, 3]  The modified T cells are typically infused 2-14 days after lymphocyte depletion. Once infused, the cells continue to expand in number and bind to cancer cells via the engineered receptor, resulting in immunologic cancer cell death. [4]  Persistence of CAR T cells for as long as 3 years has been reported. [5]


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