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. 2021 Oct 14;12:738456. doi: 10.3389/fimmu.2021.738456

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Copyright © 2021 Ghahri-Saremi, Akbari, Soltantoyeh, Hadjati, Ghassemi and Mirzaei

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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Novel strategies to boost CAR T cells efficacy against different types of tumors using genetic manipulations of different cytokines/chemokines and their receptors. (A) Incorporation of different cytokines/chemokines or their signaling domains in CAR construct. (B) Inclusion of truncated cytokine receptors lacking intracellular signaling domain. (C) Incorporation of inverted cytokine receptors (ICRs) to convert immunosuppressive signals to immunopromoting signals (D) Incorporation of membrane-tethered cytokine to provoke certain signal transduction of through its receptor. (E) Overexpression of chemokine receptors to improve CAR T cell trafficking into the tumor sites. CAR, Chimeric Antigen Receptor; TCR, T Cell Receptor; ICR, Inverted Cytokine Receptor.