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

Updated: May 04, 2018
  • Author: Sameh Gaballa, MD, MS; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Answer

CARs are synthetic proteins with 2 components: an extracellular antigen-recognizing domain, composed of fragments of monoclonal antibodies recognizing a specific protein on the surface of the malignant cells (eg, CD19 on B-cells), and an intracellular activation domain that ensures the T-cell receptor (TCR) 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 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,  CD2841BB, CD3z-CD28-41BB, CD3z-CD28-OX40) that enhances the CAR-T cells’ ability to proliferate, expand, and persist in vivoLymphocyte depletion further enhances the ability of CAR-T cells to proliferate in vivo.

The modified T-cells are typically reinfused into the patient 2-14 days after lymphocyte depletion with conditioning chemotherapy.  Once in the patient’s body, the cells continue to expand in number and bind to cancer cells via the engineered receptor, resulting in cell death. [2]  Persistence of CAR T-cells for as long as 3 years has been reported. [3]


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