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Fig. 2 | Journal of Hematology & Oncology

Fig. 2

From: Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia

Fig. 2

The four generations of CAR production. The extracellular domain of CAR includes a single chain variable fragment (scFv) (H (heavy) and L (light) chain) that is spliced by a linker. A hinge (e.g., hinge region of human immunoglobulin D molecule) ensures flexibility and connects to the transmembrane domain (TM). The TM is routinely the constant region of the human G immunoglobulin, whereas the intracellular domain includes only the CD3ζ signaling domain known as the “1st-generation CAR”. Subsequently, to augment T cell persistence and proliferation [28], CD3ζ as well as the costimulatory endo-domains 41BB- or CD28-signaling domains were incorporated into the “2nd-generation CAR”. The intracellular domain includes CD3ζ plus two costimulatory domains 41BB- and CD28-signaling domains that were included in the “3rd-generation CARs” [31, 32]. So-called TRUCK T cells are known as the “4th-generation CAR”, which is additionally modified with an inducible expression cassette for a transgenic protein

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