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• W4311227953 abstract "•Epitope-directed antibody identification aided by library and antigen design •An antibody targeting the desired Frizzled 2/7 site II region was identified •Structure-guided evolution enables the identification of highly specific variants •Epitope-specific antibodies show the expected modulations of the Wnt pathway The lack of incorporating epitope information into the selection process makes the conventional antibody screening method less effective in identifying antibodies with desired functions. Here, we developed an epitope-directed antibody selection method by designing a directed library favoring the target epitope and a precise “counter” antigen for clearing irrelevant binders in the library. With this method, we successfully isolated an antibody, pF7_A5, that targets the less conserved region on the FZD2/7 CRD as designed. Guided by the structure of pF7_A5-FZD2CRD, a further round of evolution was conducted together with the “counter” antigen selection strategy, and ultimately, an FZD2-specific antibody and an FZD7-preferred antibody were obtained. Because of targeting the predefined functional site, all these antibodies exhibited the expected modulatory activity on the Wnt pathway. Together, the method developed here will be useful in antibody drug discovery, and the identified FZD antibodies will have clinical potential in FZD-related cancer therapy. The lack of incorporating epitope information into the selection process makes the conventional antibody screening method less effective in identifying antibodies with desired functions. Here, we developed an epitope-directed antibody selection method by designing a directed library favoring the target epitope and a precise “counter” antigen for clearing irrelevant binders in the library. With this method, we successfully isolated an antibody, pF7_A5, that targets the less conserved region on the FZD2/7 CRD as designed. Guided by the structure of pF7_A5-FZD2CRD, a further round of evolution was conducted together with the “counter” antigen selection strategy, and ultimately, an FZD2-specific antibody and an FZD7-preferred antibody were obtained. Because of targeting the predefined functional site, all these antibodies exhibited the expected modulatory activity on the Wnt pathway. Together, the method developed here will be useful in antibody drug discovery, and the identified FZD antibodies will have clinical potential in FZD-related cancer therapy." @default.
• W4311227953 created "2022-12-24" @default.
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• W4311227953 date "2023-01-01" @default.
• W4311227953 modified "2023-10-18" @default.
• W4311227953 title "An epitope-directed selection strategy facilitating the identification of Frizzled receptor selective antibodies" @default.
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• W4311227953 doi "https://doi.org/10.1016/j.str.2022.11.009" @default.
• W4311227953 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36513066" @default.
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