Front. Immunol.

Sec. T Cell Biology

Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1531294

Provisionally accepted

The final, formatted version of the article will be published soon.

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Allogeneic chimeric antigen receptor T (CAR-T) therapy, also known as universal CAR-T (UCAR-T) therapy, offers broad applicability, high production efficiency, and reduced costs, enabling quicker access for patients. However, clinical application remains limited by challenges such as immune rejection, and issues with potency and durability. To address these limitations, we developed an 'all-in-one' self-activated and protective (SAP) module, integrated into the CAR scaffold. The SAP module consists of the CD47 extracellular domain, a mutant interleukin 7 receptor alpha (IL7Rα) transmembrane domain, and the IL7Rα intracellular domain, designed to protect UCAR-T cells from host immune attacks and enhance their survival. As anticipated, SAP UCAR-T cells experienced reduced immune rejection from the innate immune system, showed improved persistence and functionality both in vitro and in vivo, and raised no safety concerns. Moreover, the process stability of SAP UCAR-T cells was demonstrated in scale-up production. Overall, our findings highlight the SAP module as a promising strategy for the preclinical development of anti-CD70 UCAR-T, paving the way for an 'off-the-shelf' cell therapy product.

Keywords: chimeric antigen receptor T (CAR-T), allogeneic CAR-T, cancer immunotherapy, Solid tumor, CD70-positive cancer

Received: 20 Nov 2024; Accepted: 30 Dec 2024.

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