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This is an adaptable chimeric antigen receptor (CAR) T-cell platform designed to target solid tumors while minimizing on-target, off-tumor toxicity. The system consists of two components: T cells engineered to express a CAR specific for the cMyc peptide tag (derived from the 9E10 antibody) and a separate adaptor molecule, JZQ-B4. JZQ-B4 is a high-affinity nanobody that targets Mesothelin (MSLN) and is modified with a C-terminal cMyc tag. In practice, the JZQ-B4 adaptor binds to MSLN-expressing tumor cells, decorating the tumor surface with cMyc tags that are subsequently recognized by the cMyc CAR T cells. This modular design allows for the fine-tuning of T-cell activity through the controlled administration of the adaptor and provides a versatile framework that can be adapted to different tumor antigens by simply switching the nanobody component. Preclinical studies in lung cancer xenograft models have demonstrated that this platform achieves potent antitumor efficacy and improved safety compared to conventional, high-affinity CAR T cells.
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