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. 2023 Mar 10;12(6):2173. doi: 10.3390/jcm12062173

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© 2023 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Methods to overcome the barriers of CAR-T cells in the treatment of HNSCC. There are three aspects in overcoming the barriers including promoting CAR-T cell infiltration to the solid tumor (a–c), activation (d–f) and reducing cytotoxicity in normal cells (g,h). (a) Intratumoral injection of CAR-T cell. (b) Photothermal pre-treatment followed by CAR-T cell therapy. (c) Expression of chemokine receptor through genetic engineering. (d) Tandem CAR-T cell targeting multiply proteins. (f) Secretion of immune-checkpoint-blocking proteins through genetic engineering. (g) iCAR-T cell. (h) Expression of suicide genes. (NIR: near infrared; TanCAR-T: tandem CAR-T cells; iCAR: inhibitory CAR.