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. 2021 Dec 3;9:778020. doi: 10.3389/fcell.2021.778020

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Copyright © 2021 Skurikhin, Pershina, Zhukova, Widera, Ermakova, Pan, Pakhomova, Morozov, Kubatiev and Dygai.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Evolution of chimeric antigen receptor (CAR) from the first generation to the fourth generation. Single chain antibody (CD3ζ or FcεRIγ) links the ITAM at transmembrane region for the first generation. Costimulatory molecule (CM1), such as CD28, has been engineered to the signal transduction region for the second generation. Another costimulatory molecule (CM2) based on the second generation for the third generation has been engineered to the signal transduction region. The interleukin-12 (IL-12) based on the second generation for the fourth generation has been engineered to the signal transduction region. ITAM, Immunoreceptor tyrosine-based activation.