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. 2021 Nov 26;156(1):81–96. doi: 10.1007/s11060-021-03902-8

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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/.

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Fig. 1 — CAR-T design and current generations. A The basic CAR-T architecture consists of a target domain followed by a stem or hinge, a transmembrane domain and intracellular co-stimulatory motifs. Tags for easy identification can be placed in different key locations as shown. B Several types of co-stimulatory domain targets have been characterized to be used with CAR-T. C CAR-T have experienced a fast evolution, from the initial First Generation (First Gen) comprising only one stimulatory domain, all the way to second, third, fourth and next-generation CARs, comprising several combinations of co-stimulatory domain molecules as well as JAK/STAT signaling (Next-Gen)