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- W2891096931 abstract "Secreted Wnt ligands play a major role in the development and progression of many cancers by modulating signaling through cell-surface Frizzled receptors (FZDs). In order to achieve maximal effect on Wnt signaling by targeting the cell surface, we developed a synthetic antibody targeting six of the 10 human FZDs. We first identified an anti-FZD antagonist antibody (F2) with a specificity profile matching that of OMP-18R5, a monoclonal antibody that inhibits growth of many cancers by targeting FZD7, FZD1, FZD2, FZD5 and FZD8. We then used combinatorial antibody engineering by phage display to develop a variant antibody F2.A with specificity broadened to include FZD4. We confirmed that F2.A blocked binding of Wnt ligands, but not binding of Norrin, a ligand that also activates FZD4. Importantly, F2.A proved to be much more efficacious than either OMP-18R5 or F2 in inhibiting the growth of multiple RNF43-mutant pancreatic ductal adenocarcinoma cell lines, including patient-derived cells." @default.
- W2891096931 created "2018-09-27" @default.
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- W2891096931 date "2018-09-25" @default.
- W2891096931 modified "2023-10-01" @default.
- W2891096931 title "A synthetic anti-Frizzled antibody engineered for broadened specificity exhibits enhanced anti-tumor properties" @default.
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- W2891096931 doi "https://doi.org/10.1080/19420862.2018.1515565" @default.
- W2891096931 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6284576" @default.
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