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. 2022 Mar 22;12:832765. doi: 10.3389/fonc.2022.832765

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Copyright © 2022 Miao, Zhang, Huang, Zhang, Wang, Tang, Teng and Li

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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Some conjectures about CARs containing three scFvs. (A) Connecting three scFvs in tandem. (B) In dual-signaling CARs, one CAR is replaced by a TanCAR. (C) One of the dual-signaling CARs is replaced with a TanCAR, and the other is upgraded to a fourth-generation CAR. (D) Both CARs in dual-signaling CAR are replaced with tandem CARs. (E) At first, synNotch 1 receptor is activated after binding to tumor antigen (a), and the activated synNotch 1 receptor induces the expression of synNotch 2 receptor. Then synNotch 2 receptor binds to tumor antigen (b), which induces the expression of c-CAR; c-CAR can bind to the tumor antigen (c); finally, the CAR-T cell is activated.