ArticleFrontiers in immunology2025
Improvement in the function of self-activating chimeric antigen receptor by replacing the linker sequence.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Non-signaling but all important: how the linker, hinge, and transmembrane domains in the CAR hold it all together.Frontiers in immunology · 2025Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR)-T cell therapy is an effective treatment for hematological cancers; however, challenges remain in its application to solid tumors. Among these, the control of CAR-T cell exhaustion is important. The relationship between tonic signals generated by the CAR self-activation and CAR-T cell exhaustion has attracted considerable attention. The magnitude of the tonic signal is known to depend on the structure of the extracellular portion of CAR, but the role of the linker sequence of the single-chain variable region (scFv) in the tonic signal and function in CAR-T cells has not been clarified. In this study, we compared two scFv linkers, G4S and Whitlow/218, in self-activating SKM-CAR, which recognized a malignant mesothelioma-specific modified HEG1 molecule. We observed no differences in cell surface phenotypes, NFAT and NFκB signaling intensities, and gene expression profiles between SKM-CAR T cells with these different linkers. However, switching from the G4S to the Whitlow/218 linker in SKM-CAR-T cells with the CD28 co-stimulatory domain significantly altered cytokine expression after antigen stimulation and improved the
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