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The Anti-LeY-scFv-CD28-ζ vector is a chimeric antigen receptor (CAR) construct used in CAR T-cell therapy targeting the Lewis Y (LeY) antigen. This vector contains three main components: an anti-LeY single-chain variable fragment (scFv) for antigen recognition, a CD28 costimulatory domain, and a CD3ζ signaling domain. The vector is designed to be transduced into T cells, creating CAR T cells that can specifically target cells expressing the LeY antigen. The LeY antigen is an oligosaccharide overexpressed on many epithelial cancers and hematological malignancies, including acute myeloid leukemia (AML), but has limited expression on normal healthy tissues[1][5]. When the scFv domain binds to LeY on target cells, it triggers T cell activation through the CD28 costimulatory domain and CD3ζ signaling domain, leading to cytokine production (including IFN-γ and IL-2), T cell proliferation, and cytotoxic activity against LeY-expressing tumor cells[1][5]. This represents a second-generation CAR design, which provides both primary activation signals (via CD3ζ) and costimulatory signals (via CD28) to enhance T cell function, proliferation, and persistence compared to first-generation CARs that contained only CD3ζ[6][8].
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