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CD37.18aaL CAR-T is an experimental third-generation chimeric antigen receptor (CAR) T-cell therapy designed to target CD37, a glycoprotein expressed on the surface of mature B-cells and certain T-cell malignancies. Developed by researchers at Prince of Songkla University and Nagoya University, this construct is distinguished by its use of a specific 18-amino acid glycine-serine linker (GSTSGSGKPGSGEGSTKG) within the single-chain variable fragment (scFv). The CAR architecture includes dual costimulatory domains, CD28 and CD40, alongside the CD3-zeta signaling domain and a truncated EGFR (tEGFR) marker for cell enrichment. Preclinical evaluations presented at ASH 2023 compared this 18aaL variant to a standard GS4L linker version, finding that the 18aaL construct exhibited lower binding affinity, reduced expansion, and increased autologous T-cell killing (fratricide), suggesting that linker flexibility significantly impacts CAR-T performance against CD37-positive malignancies such as lymphoma and leukemia.
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