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CD8 hinge & TM CD70 CAR-T (formally trCD27-CD8H&TM-41BB-CD3ζ) is a second-generation, ligand-based chimeric antigen receptor (CAR) T-cell therapy engineered to target CD70, a tumor-associated antigen prevalent in myeloid malignancies. Developed at Massachusetts General Hospital, the construct features an extracellular binding domain derived from truncated CD27, the natural ligand for CD70. To address the issue of decapitation (protease-mediated cleavage of the CAR from the cell surface), the native CD27 hinge and transmembrane regions were replaced with those from CD8α. This modification significantly enhances binding avidity, T-cell expansion, and in vivo anti-tumor efficacy. The CAR incorporates a 4-1BB costimulatory domain and a CD3ζ signaling domain, and it has demonstrated potent activity in preclinical models of acute myeloid leukemia (AML) and multiple myeloma.
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