CAR spacers: not just filling space

Date

2024

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Brown, M.P.

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Journal article

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Molecular Therapy, 2024; 32(10):3207-3208

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Abstract

A growing and sizable literature indicates that the chimeric antigen receptor (CAR)-T cell spacer is not merely an inert protein sequence between the binding ectodomain and the transmembrane component of the CAR molecule. CAR spacers have important structural and functional properties. Although spacers are not an integral part of the intracellular signaling machinery, they may, as illustrated in this issue of Molecular Therapy, have an indirect effect on cellular signaling outputs.1 Kua et al. show that a novel 25-mer spacer derived from the extracellular domain of the T cell co-stimulatory molecule 4-1BB maintained the potency of CD30-directed CAR-T cell killing while resulting in lower levels of inflammatory cytokines, unlike the original wild-type immunoglobulin (Ig)G1 spacer. Further comparative studies should elucidate the potential clinical utility of this novel CAR spacer.

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Copyright 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

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