CAR T Cell Therapy: A Game Changer in Cancer Treatment

Figure 1

Elements involved in TCR and CAR recognition and activation. The TCR is disulfide-linked heterodimer consisting of one α and one β chain expressed in complex with invariant CD3 chains (, and ). The TCR recognizes intracellular or extracellular proteins presented as peptides by MHC molecules. Costimulation of CD28 through its ligands, CD80/CD86, is required for optimal activation and production of interleukin-2 (IL-2) and other cytokines. While most hematological tumors express costimulatory molecules, solid tumor cells as well as antigen presenting cells in the tumor microenvironment usually lack such molecules. CARs recognize surface antigens in an MHC unrestricted manner. CARs are fusion proteins between single-chain variable fragments (scFv) from a monoclonal antibody and one or more T cell receptor intracellular signaling domains. Various hinges and transmembrane (TM) domains are used to link the recognition and the signaling molecules [5]. While first generation CARs signaled through the CD3ζ chain only, second generation CARs include a signaling domain from a costimulatory molecule, for example, CD28 (illustrated), 4-1BB, OX40, CD27, or ICOS.