{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(1)"],"submitter":["Foss S"],"funding":["Wellcome Trust"],"pubmed_abstract":["Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions."],"journal":["Nature communications"],"pagination":["2007"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10920689"],"repository":["biostudies-literature"],"pubmed_title":["Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria."],"pmcid":["PMC10920689"],"pubmed_authors":["Ram S","Andersen JT","Evers M","Michaelsen TE","Rooijakkers SHM","Shaughnessy J","Leusen J","Sok D","Ruso-Julve F","Mathiesen L","Sakya SA","Mester S","Bern M","Scheepmaker L","Cruz AR","Schlothauer T","Lustig M","Aguinagalde L","Anthi AK","Bratlie DB","Valerius T","Foss S","Sandlie I","Gjolberg TT","Bhattacharya J"],"additional_accession":[]},"is_claimable":false,"name":"Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria.","description":"Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-07-15T12:08:02.488Z","creation":"2026-07-04T03:12:44.028Z"},"accession":"S-EPMC10920689","cross_references":{"pubmed":["38453922"],"doi":["10.1038/s41467-024-46321-9"]}}