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• W4386802553 abstract "As a highly lethal adenocarcinoma of the hepatobiliary system, outcomes for cholangiocarcinoma (CCA) patients remain prominently poor with a 5-year survival of <10% due to the lack of effective treatment modalities. Targeted therapeutics for CCA are limited and surgical resection of CCA frequently suffers from a high recurrence rate. Here we report two effective targeted therapeutics in this preclinical study for CCA. We first performed a quantitative and unbiased screening of cancer-related antigens using comparative flow cytometry in a panel of human CCA cell lines, and identified intercellular adhesion molecule-1 (ICAM1) as a therapeutic target for CCA. After determining that ICAM1 has the ability to efficiently mediate antibody internalization, we constructed two ICAM1 antibody-drug conjugates (ADCs) by conjugating ICAM1 antibodies to different cytotoxic payloads through cleavable chemical linkers. The efficacies of two ICAM1 ADCs have been evaluated in comparison with the first-line chemodrug Gemcitabine in vitro and in vivo, and ICAM1 antibodies coupled with warhead DX-8951 derivative (DXd) or monomethyl auristatin E (MMAE) elicit a potent and consistent tumor attenuation. In summary, this study paves the road for developing a promising targeted therapeutic candidate for clinical treatment of CCA." @default.
• W4386802553 created "2023-09-17" @default.
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• W4386802553 date "2023-09-16" @default.
• W4386802553 modified "2023-09-26" @default.
• W4386802553 title "Development of potent antibody drug conjugates against ICAM1+ cancer cells in preclinical models of cholangiocarcinoma" @default.
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• W4386802553 doi "https://doi.org/10.1038/s41698-023-00447-z" @default.
• W4386802553 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37717087" @default.
• W4386802553 hasPublicationYear "2023" @default.
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