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TAG72-BBζ CAR T cells are second-generation chimeric antigen receptor T cells engineered to target **tumor-associated glycoprotein 72 (TAG72)**, a sialyl-Tn antigen highly expressed on the surface of ovarian and other epithelial cancers[2][3]. The CAR construct incorporates a humanized single-chain variable fragment (scFv) (often CC49), an IgG4 Fc extracellular spacer lacking the CH2 domain, a transmembrane domain (often CD4 or CD28), a 4-1BB (CD137) intracellular co-stimulatory domain, and a CD3ζ cytolytic domain for T cell activation and cytotoxicity[2][1]. These T cells demonstrate **potent, antigen-dependent cytotoxicity and cytokine production (IFNγ, IL-2)** against TAG72+ tumor cells. Local (intraperitoneal) administration leads to significant anti-tumor activity in preclinical models of ovarian cancer, with enhanced responses observed upon repeat dosing[2][3]. Developed primarily for advanced ovarian cancer, they are under phase 1 clinical evaluation[1]. The use of the 4-1BB domain improves persistence and reduces T cell exhaustion, addressing limitations of first-generation CAR T designs[2].
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