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- W4313358905 abstract "Abstract Natural killer (NK) cells are a type of cytotoxic lymphocytes critical to immune surveillance. The mechanisms for NK-mediated tumor elimination including natural cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC), and the secretion of interferon-γ (IFN-γ), which are essential for mediating the anti-tumor activity. CD19, a B-cell lineage-specific marker, is highly expressed in B-cell malignancies and an attractive target for therapy. Here, we generate a trifunctional bispecific antibody (TBAb) containing single chain antibody fragment (scFV) against CD16 and CD19 to create an immunologic synapse between NK cells and CD19+ lymphoma cells. X has been engineered with a modified human interleukin crosslinker for improving therapeutic efficacy. Specificity has been confirmed by investigating the ability of X to bind CD19+ tumor targets and CD16+ NK cells. We found that X TBAb mediated killing of human lymphoma B cell lines, including namalwa, daudi and raji, by human NK cells purified by microbeads or NK-cell amplification kit in vitro. X-mediated killing is accompanied by NK-cell activation, cytokine release and upregulation of TNF-related apoptosis-inducing ligand (TRAIL). Further, X TBAb demonstrated antitumor activity against lymphoma xenografts reconstituted with human PBMCs. These data provide a therapeutic candidate for the treatment of B-cell malignancies." @default.
- W4313358905 created "2023-01-06" @default.
- W4313358905 creator A5027325514 @default.
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- W4313358905 date "2020-05-01" @default.
- W4313358905 modified "2023-10-01" @default.
- W4313358905 title "A trifunctional bispecific antibody mediates efficient killing of B-cell lymphoma cells" @default.
- W4313358905 doi "https://doi.org/10.4049/jimmunol.204.supp.169.6" @default.
- W4313358905 hasPublicationYear "2020" @default.
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