Chymeric Antigen Receptor

Chimeric antigen receptors, or CARs, are recombinant receptors composed of an extracellular single-chain variable fragments (scFv) derived from an antibody, joined to a hinge/spacer peptide and a transmembrane domain, which is further linked to the intracellular T cell signaling domains of the T cell receptor. CAR T cells combine the specificity of an antibody with the cytotoxic and memory functions of T cells

CAR-T components:

Target Element The single-chain variable fragment (scFv) is expressed on the surface of a CAR T cell and confers antigen specificity. The scFv is derived from the portion of an antibody that specifically recognizes a target protein.2, 4

Transmembrane Domain. The transmembrane domain traverses the cell membrane, anchors the CAR to the cell surface, and connects the extracellular domain to the intracellular signaling domain, thus impacting expression of the CAR on the cell surface.2

Costimulatory Domain. The costimulatory domain is derived from the intracellular signaling domains of costimulatory proteins, such as CD28 and 4-1BB, that enhance cytokine production.1, 3

Signaling Domain. The CD3 zeta domain is derived from the intracellular signaling portion of the T cell receptor, which mediates downstream signaling during T cell activation.3, 4

Spacer. The spacer connects the extracellular targeting element to the transmembrane domain and affects CAR function and scFv flexibility.4

References

1.  Maus MV, Levine BL. Chimeric antigen receptor T cell therapy for the community oncologist. The Oncologist. 2016;21:1-10.
2.  Abate-Daga D, Davila ML. CAR models: next-generation CAR modifications for enhanced T-cell function. Mol Ther Oncolytics. 2016 May 18;3:16014.
3.  Abate-Daga D, Davila ML. CAR models: next-generation CAR modifications for enhanced T cell function. Mol Ther Oncolytics. 2016;3:16014.   doi: 10.1038/mto.2016.14.
4.  Dai H, Wang Y, Lu X, Han W. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy. J Natl Cancer Inst. 2016 Jan 27;108(7). pii: djv439

T Cell Receptor (TCR) Technology: coming soon