ArticleEJNMMI research2016
Engineering anti-Lewis-Y hu3S193 antibodies with improved therapeutic ratio for radioimmunotherapy of epithelial cancers.
Article in EJNMMI research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Preclinical evaluation of an antibody-based companion diagnostic for CD44v6 expressing cancer.Nuclear medicine communications · 2026Article
- Preclinical Validation of [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Engineered Antibodies as Cancer Radiotheranostics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- TRIM21 and Fc-engineered antibodies: decoding its complex antibody binding mode with implications for viral neutralization.Frontiers in immunology · 2024Article
- Antibody Engineering for Nuclear Imaging and Radioimmunotherapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
- An N-glycoproteomic site-mapping analysis reveals glycoprotein alterations in esophageal squamous cell carcinoma.Journal of translational medicine · 2022Article
- Identification of Targets to Redirect CAR T Cells in Glioblastoma and Colorectal Cancer: An Arduous Venture.Frontiers in immunology · 2020Review
- TSTA3 facilitates esophageal squamous cell carcinoma progression through regulating fucosylation of LAMP2 and ERBB2.Theranostics · 2020Article
- High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC.Technology in cancer research & treatment · 2018Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundThe 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.
methodsFour 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(111)In-labelled I253A and H435A showed similar slow kinetics (t 1/2β, 63.2 and 62.2 h, respectively) and a maximum tumour uptake of 33.11 ± 4.05 and 33.69 ± 3.77 percentage injected dose per gramme (%ID/g), respectively. (111)In-labelled I253A/H310A cleared fastest (t 1/2β, 9.1 h) with the lowest maximum tumour uptake (23.72 ± 0.85 %ID/g). The highest increase in tumour-to-blood area under the curve (AUC) ratio was observed with the metal-labelled mutants ((90)Y and (177)Lu). (177)Lu-CHX-A" DTPA-hu3S193 I253A/H310A (6:1) showed the highest tumour-to-blood AUC ratio compared to wild type (3:1) and other variants and doubling of calculated dose to tumour based on red marrow dose constraints.
conclusionsThese results suggest that hu3S193 Fc can be engineered with improved therapeutic ratios for (90)Y- and (177)Lu-based therapy, with the best candidate being hu3S193 I253A/H310A for (177)Lu-based therapy.
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