biostudies-literatureRiley CJNCI NIH HHS1933-40https://www.ebi.ac.uk/biostudies/studies/S-EPMC2672909biostudies-literatureUnknown69(5)Pancreatic ductal adenocarcinoma (PDA) is a lethal disease, with surgery being the only curative modality for localized disease, and gemcitabine with or without erlotinib remains the standard of therapy for unresectable or metastatic disease. CEACAM6 is overexpressed in human PDA independent of stage or grade and causes anoikis resistance when dysregulated. Because murine monoclonal antibody 13-1 possesses target-specific cytotoxicity in human PDA cell lines, we designed a humanized anti-CEACAM6 single-chain variable fragment (scFv) based on monoclonal antibody 13-1. PEGylation of the glycine-serine linker was used to enhance plasma half-life. These scFvs bound CEACAM6 with high affinity, exhibited cytotoxic activity, and induced dose-dependent poly(ADP-ribose) polymerase cleavage. Murine Cancer researchDesign and activity of a murine and humanized anti-CEACAM6 single-chain variable fragment in the treatment of pancreatic cancer.PMC2672909P50 CA095060-03P30 CA023074P50 CA095060CA23074CA95060-03Saldanha JWShakalya KZhu YGeorgiev IGMahadevan DQi WNarayan STCooke LSEngelhardt KPCroce KDNagle RBGarewal HRiley CJVon Hoff DDfalseDesign and activity of a murine and humanized anti-CEACAM6 single-chain variable fragment in the treatment of pancreatic cancer.Pancreatic ductal adenocarcinoma (PDA) is a lethal disease, with surgery being the only curative modality for localized disease, and gemcitabine with or without erlotinib remains the standard of therapy for unresectable or metastatic disease. CEACAM6 is overexpressed in human PDA independent of stage or grade and causes anoikis resistance when dysregulated. Because murine monoclonal antibody 13-1 possesses target-specific cytotoxicity in human PDA cell lines, we designed a humanized anti-CEACAM6 single-chain variable fragment (scFv) based on monoclonal antibody 13-1. PEGylation of the glycine-serine linker was used to enhance plasma half-life. These scFvs bound CEACAM6 with high affinity, exhibited cytotoxic activity, and induced dose-dependent poly(ADP-ribose) polymerase cleavage. Murine 2009-01-01T00:00:00Z2009 Mar2025-04-26T17:39:56.953Z2019-03-27T00:21:59ZS-EPMC26729091924412310.1158/0008-5472.CAN-08-270710.1158/0008-5472.can-08-2707