CAR T
Published on April 03, 2025
Studying the anti-tumor efficacy of a novel chimeric receptor, D-STAR
by Nature Medicine
Yu L, Zhou Z, Yu H, et al. Converting TCR-Based Chimeric Antigen Receptor STAR Into Dual-Specific Targeting Receptor for Cancer Immunotherapy. Molecular Therapy. 2025; (doi: 10.1016/j.ymthe.2025.02.001).
Developers are encouraged by the robust anti-tumor potency demonstrated by their novel chimeric receptor, the Dual-targeting Synthetic TCR and Antigen Receptor (D-STAR). The new construct is structurally superior to single and dual-targeting chimeric antigen receptor (CAR)-T cells, activating T cells and triggering effector functions in response to stimulation by a single antigen. Multi-specific traditional CAR engineering, in contrast, demands precisely ordered single-chain variable fragments, with aggregation problems often arising with linear assembly. D-STAR's aggressive killing of various malignant B cells outperformed the antitumor efficacy of single- and dual-targeting CAR-T cells, based on murine models. Integrating the OX40 costimulatory cytoplasmic domain with flexible linkers further boosted D-STAR's efficacy.
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