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. 2021 Aug 20;12:465. doi: 10.1186/s13287-021-02420-8

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Different generations of CAR T cells. CAR signaling and applications are updated with each new generation. The first generation consists of an intracellular domain (CD3ζ chain), the second generation of CAR T cells has been composed of the addition of CD28 to CD3 as co-stimulatory molecules. In the third generation of CAR T cells, OX-40, a second co-stimulatory molecule, has been added. In the fourth generation, NFAT has been added to the induction of cassette containing the IL-12 gene promoter. NFAT, nuclear factor of activated T cells