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. Author manuscript; available in PMC: 2021 Feb 1.
Published in final edited form as: Cytotherapy. 2020 Feb 1;22(2):57–69. doi: 10.1016/j.jcyt.2019.12.004

Figure 2. Evolution of chimeric antigen receptors.

Figure 2.

CAR, chimeric antigen receptor. a. First concept of chimeric gene constructs of T cell receptor (TCR) constant regions (Cα and Cβ) fused to immunoglobulin (Ig) variable regions, VH and VL. In the “pre-CAR” concept formation of the antigen recognizing domain VH-VL required pairing of two individual constructs. b. Chimeras of CD4 and other surface molecules are engrafted onto the CD3ζ or Fcγ signaling domains originally with the purpose of elucidating the function of CD3ζ and Fcγ. c. The ”T-body” as proposed by Dr. Eshhar. The variable antibody domains VL and VH are put in serial connection via a linker creating a single chain variable fragment (scFv). The scFv is connected via a hinge to either a CD3ζ or the Fc receptor γ (FcRγ) activating domain. d. and e. Addition of a costimulatory molecule (e.g. CD28 or 4-1BB as shown in figure) established “second-generation CARs”.