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FIGURE 21.2
Evolution of chimeric antigen receptors. First-generation chimeric antigen receptors (CARs) consist of an extracellular domain encoding a single-chain immunoglobu-
lin specific for tumor antigen, an immunoglobulin transmembrane region, and an intracellular domain encoding the human CD3- ζ protein. This CAR allows for specific
recognition of tumor antigens by T cells without the need for MHC processing and presentation. Second-generation CARs improved T-cell expansion by incorporating a
costimulatory signaling domain into the CD3- ζ portion of the construct. Using CAR T cells specific for CD19, this approach was clinically effective against chemotherapy-
refractory chronic lymphocytic leukemia in three patients. Third-generation CARs include combinations of multiple costimulatory domains. (From: Urba W J, Longo D L. N
Engl J Med 2011; 365: 754. Used with permission from the Massachusetts Medical Society.)