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ROR1 Hinge CAR-T is a second-generation chimeric antigen receptor (CAR) T-cell therapy designed to target Receptor tyrosine kinase-like orphan receptor 1 (ROR1), an oncofetal glycoprotein overexpressed in various hematological and solid malignancies. The CAR construct utilizes a single-chain variable fragment (scFv) derived from the humanized monoclonal antibody zilovertamab (formerly cirmtuzumab), which binds to a distal extracellular epitope of ROR1. It features a short IgG4 hinge spacer region, which has been shown to provide superior surface expression and in vitro functionality compared to longer spacers. The intracellular signaling architecture includes a 4-1BB costimulatory domain and a CD3zeta activation domain. Preclinical data indicate potent anti-tumor activity against mantle cell lymphoma, lung cancer, and breast cancer models without significant in vivo toxicity.
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