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- W3136942841 abstract "Abstract Purpose Multiple myeloma (MM) is the second most common hematological malignancy, and B-cell maturation antigen (BCMA) is a highly regarded target of MM research. In tumors, the natural killer (NK) cell receptor NK group 2, member D (NKG2D), and its ligand MHC class I-related chain A (MICA) play important roles in immune surveillance and killing. We developed a bispecific fusion protein (BFP) that targeted NKG2D and BCMA, which may be useful for the MM therapeutic market. Methods The Homo MICA extracellular domains (hMICA) α1-3 or α1-2 were fused to the end of the single chain antibody (ScFv) 2A9 with the flexible linker (G4S), which formed 2A9-MICA and 2A9-MICAα1-2. These were further identified using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting (WB). The dual-targeting specificity was characterized using Surface Plasmon Resonance (SPR) technology and a flow cytometry assay. In addition, a cytotoxicity assay showed that the design of BFP mediated the lysis of MM cells. Further, in MM-bearing nude mice, the anti-tumor effect and the ability to activate NK cells within tumor tissues of BFP were verified. Results Compared with 2A9-MICA, 2A9-MICAα1-2 had a stronger affinity to BCMA and NKG2D, which mediated cytotoxicity of NK effector cells against MM cells. In vivo , 2A9-MICAα1-2 showed superior anti-MM efficacy, significantly reduced malignancy, effectively activated CD56 + TNF-α + NK cells, and promoted immune infiltration within the tumor environment. Conclusion After we evaluated aspects of 2A9-MICA and 2A9-MICAα1-2 comprehensively, we concluded that 2A9-MICAα1-2 deserves further study and investigation, and it provides a possible strategy for immunotherapy that targets MM." @default.
- W3136942841 created "2021-03-29" @default.
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- W3136942841 date "2021-03-23" @default.
- W3136942841 modified "2023-10-17" @default.
- W3136942841 title "BCMA targets bispecific fusion protein for induction of NK cell activity against multiple myeloma" @default.
- W3136942841 doi "https://doi.org/10.21203/rs.3.rs-351031/v1" @default.
- W3136942841 hasPublicationYear "2021" @default.
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