Journal article
Engineering anti-Lewis-Y hu3S193 antibodies with improved therapeutic ratio for radioimmunotherapy of epithelial cancers
IJG Burvenich, FT Lee, GJ O’Keefe, D Makris, D Cao, S Gong, A Rigopoulos, LC Allan, MW Brechbiel, Z Liu, PA Ramsland, AM Scott
Ejnmmi Research | Published : 2016
Abstract
Background: The aim of the study was to explore Fc mutations of a humanised anti-Lewis-Y antibody (IgG1) hu3S193 as a strategy to improve therapeutic ratios for therapeutic payload delivery. Methods: Four hu3S193 variants (I253A, H310A, H435A and I253A/H310A) were generated via site-directed mutagenesis and radiolabelled with diagnostic isotopes iodine-125 or indium-111. Biodistribution studies in Lewis-Y-positive tumour-bearing mice were used to calculate the dose in tumours and organs for therapeutic isotopes (iodine-131, yttrium-90 and lutetium-177). Results: 111In-labelled I253A and H435A showed similar slow kinetics (t1/2β, 63.2 and 62.2 h, respectively) and a maximum tumour uptake of 3..
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Awarded by Ludwig Institute for Cancer Research
Funding Acknowledgements
This research was supported by National Health and Medical Research Council Project Grants 542512, 1030469, National Health and Medical Research Council Program grant 487922, National Health and Medical Research Council Practitioner Fellowship (A.M.S.), and in part by Ludwig Cancer Research, by funds from the Operational Infrastructure Support Program provided by the Victorian Government, and the Intramural Research Program of the NIH, National Cancer Institute, Centre for Cancer Research.