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2G-EDB CAR is a second-generation chimeric antigen receptor (CAR) T-cell therapy targeting the extra domain B (EDB) of fibronectin. EDB-fibronectin is an oncofetal isoform of fibronectin that is highly expressed in the neovasculature and stroma of various solid tumors but is virtually absent in normal adult tissues. The 2G-EDB CAR construct consists of an EDB-specific single-chain variable fragment (scFv) fused to a CD28 costimulatory domain and a CD3ζ signaling domain. In preclinical studies, 2G-EDB CAR T cells demonstrated cytotoxicity against EDB-positive cell lines such as U87MG (glioblastoma) and A549 (lung cancer) in vitro. However, its in vivo efficacy in xenograft models was found to be moderate, leading to the development of more advanced iterations like the 3ε28-EDB CAR, which incorporates the CAR into the T-cell receptor (TCR) complex for enhanced signaling and tumor regression.
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