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- W4387336351 abstract "Antibody-mimetic drug conjugate (AMDC) is a cancer cell-targeted drug delivery system based on the non-covalent binding of mutated streptavidin and modified biotin, namely Cupid and Psyche. However, the development of AMDCs is hampered by difficulties in post-translational modification or poor internalization activity. Here, we report an expression, refolding, and purification method for AMDC using a variable heavy chain of heavy chain-only antibodies (VHHs). Monomeric anti-HER2 VHH fused to Cupid was expressed in Escherichia coli inclusion bodies. Solubilization and refolding at optimized reducing conditions and pH levels were selected to form a functional, tetrameric protein (anti-HER2 VHH-Cupid) that can be easily purified based on molecular weight. Anti-HER2 VHH-Cupid non-covalently creates a tight complex with Cupid linked to a potent DNA-alkylating agent, duocarmycin. This complex can be absorbed by the HER2-expressing human breast cancer cell line, KPL-4, and kills KPL-4 cells in vitro and in vivo. The production of a targeting protein with internalizing activity, combined with the non-covalent conjugation of a highly potent payload, renders AMDC a promising platform for developing cancer-targeted therapy." @default.
- W4387336351 created "2023-10-05" @default.
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- W4387336351 date "2023-10-01" @default.
- W4387336351 modified "2023-10-16" @default.
- W4387336351 title "Antibody-mimetic drug conjugate with efficient internalization activity using anti-Her2 VHH and duocarmycin" @default.
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- W4387336351 doi "https://doi.org/10.1016/j.pep.2023.106375" @default.
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