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Fig. 1 | Journal of Hematology & Oncology

Fig. 1

From: A new insight in chimeric antigen receptor-engineered T cells for cancer immunotherapy

Fig. 1

Schematic diagram of TCR- and CAR-modified T cells in adoptive T cells therapy. a Activation, proliferation, and cytotoxicity of the T cell are dependent upon the dual signal pathway that includes the T cell receptors (TCRs) that recognize peptide antigens which were processed by the antigen-presenting cells and presented upon the major histocompatibility complex (MHC) of a target cells, and the costimulatory receptor of T cell simultaneously engages a ligand, such as CD28 and B7 molecules. b The first-generation CAR contains only the antigen recognition signal, CD3ζ domain, resulting in the transient activation and proliferation of the CAR-T cell based on scFv specificity. cd The second- and third-generation CARs contain one and two additional costimulatory signaling domains, respectively, such as CD28, CD137 (4-1BB), and CD134 (OX40). The costimulatory signaling domains can facilitate greater proliferation of modified-T cell and greater cytotoxicity than first-generation CAR. e To significantly enhance the overall cytotoxicity of the modified-T cell, the fourth-generation CAR-T cell is generally modified to express CARs with an inducible cytokine genes, such as IL-12 or heparinase, which can stimulate T cell to reach the surface of tumor cells in degrading the extracellular matrix (ECM) within the tumor microenvironment and blocking the inhibitory signaling pathway. f The next-generation structure of the CARs with effective specificity for target cells lacking several side effects to the body will be generated in the near future, including reconstruction of endogenous structure and introduction of exogenous regulatory

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