ArticleOncotarget2018
Structural considerations for functional anti-EGFR × anti-CD3 bispecific diabodies in light of domain order and binding affinity.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Design and Evaluation of Domain-Rearranged Bispecific Antibody Fragments for Functional Optimization.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Design of Crosslinking Antibodies For T-Cell Activation: Experimental and Computational Analysis of PD-1/CD137 Bispecific Agents.The AAPS journal · 2024Article
- c-MET and the immunological landscape of cancer: novel therapeutic strategies for enhanced anti-tumor immunity.Frontiers in immunology · 2024Review
- Cancer therapeutic trispecific antibodies recruiting both T and natural killer cells to cancer cells.Oncology reports · 2023Article
- Identifying highly active anti-CCR4 CAR T cells for the treatment of T-cell lymphoma.Blood advances · 2023Article
- Development of a reporter gene method to measure the bioactivity of anti-CD38 × CD3 bispecific antibody.Antibody therapeutics · 2021Article
- Bispecific antibodies targeting mutantScience immunology · 2021Article
- Functional Domain Order of an Anti-EGFR × Anti-CD16 Bispecific Diabody Involving NK Cell Activation.International journal of molecular sciences · 2020Article
- Development of bispecific antibodies in China: overview and prospects.Antibody therapeutics · 2020Review
- Build-up functionalization of anti-EGFR × anti-CD3 bispecific diabodies by integrating high-affinity mutants and functional molecular formats.Scientific reports · 2020Article
- Format and geometries matter: Structure-based design defines the functionality of bispecific antibodies.Computational and structural biotechnology journal · 2020Review
- The Latest Battles Between EGFR Monoclonal Antibodies and Resistant Tumor Cells.Frontiers in oncology · 2020Review
- Engineering the hinge region of human IgG1 Fc-fused bispecific antibodies to improve fragmentation resistance.Scientific reports · 2018Article
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously reported a functional humanized bispecific diabody (bsDb) that targeted EGFR and CD3 (hEx3-Db) and enhancement of its cytotoxicity by rearranging the domain order in the V domain. Here, we further dissected the effect of domain order in bsDbs on their cross-linking ability and binding kinetics to elucidate general rules regarding the design of functional bsDbs. Using Ex3-Db as a model system, we first classified the four possible domain orders as anti-parallel (where both chimeric single-chain components are variable heavy domain (VH)-variable light domain (VL) or VL-VH order) and parallel types (both chimeric single-chain components are mixed with VH-VL and VL-VH order). Although anti-parallel Ex3-Dbs could cross-link the soluble target antigens, their cross-linking ability between soluble targets had no correlation with their growth inhibitory effects. In contrast, the binding affinity of one of the two constructs with a parallel-arrangement V domain was particularly low, and structural modeling supported this phenomenon. Similar results were observed with E2x3-Dbs, in which the V region of the anti-EGFR antibody clone in hEx3 was replaced with that of another anti-EGFR clone. Only anti-parallel types showed affinity-dependent cancer inhibitory effects in each molecule, and E2x3-LH (both components in VL-VH order) showed the most intense anti-tumor activity
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