ArticleThe Journal of biological chemistry2014
A novel glycoengineered bispecific antibody format for targeted inhibition of epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor type I (IGF-1R) demonstrating unique molecular properties.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Article
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- Single-chain Fab chain-exchange (scFab-PACE) converts targeted prodrugs into functional T cell engagers on tumor cells.The Journal of biological chemistry · 2025Article
- From Cell Clones to Recombinant Protein Product Heterogeneity in Chinese Hamster Ovary Cell Systems.International journal of molecular sciences · 2025Review
- Discovery of a common light chain bispecific antibody targeting PD-1 and PD-L1 by Hybridoma-to-Phage-to-Yeast (H2PtY) platform.Antibody therapeutics · 2025Article
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
- Recombinant antibodies aggregation and overcoming strategies in CHO cells.Applied microbiology and biotechnology · 2022Review
- A new approach to produce IgGScientific reports · 2021Article
- Bioassay Development for Bispecific Antibodies-Challenges and Opportunities.International journal of molecular sciences · 2021Review
- The renaissance of chemically generated bispecific antibodies.Nature reviews. Chemistry · 2021Review
- FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer.International journal of molecular sciences · 2021Review
- Design of a Trispecific Checkpoint Inhibitor and Natural Killer Cell Engager Based on a 2 + 1 Common Light Chain Antibody Architecture.Frontiers in immunology · 2021Article
- Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers.Frontiers in cell and developmental biology · 2021Review
- Bispecific Antibodies and Antibody-Drug Conjugates for Cancer Therapy: Technological Considerations.Biomolecules · 2020Review
- Biology drives the discovery of bispecific antibodies as innovative therapeutics.Antibody therapeutics · 2020Review
- Conjugation of an scFab domain to the oligomeric HIV envelope protein for use in immune targeting.PloS one · 2019Article
- Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018Review
- Review
- BiHC, a T-Cell-Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells.Translational oncology · 2017Article
- Tethered-variable CL bispecific IgG: an antibody platform for rapid bispecific antibody screening.Protein engineering, design & selection : PEDS · 2017Article
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Authors and funding
16 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the present study, we have developed a novel one-arm single chain Fab heterodimeric bispecific IgG (OAscFab-IgG) antibody format targeting the insulin-like growth factor receptor type I (IGF-1R) and the epidermal growth factor receptor (EGFR) with one binding site for each target antigen. The bispecific antibody XGFR is based on the "knob-into-hole" technology for heavy chain heterodimerization with one heavy chain consisting of a single chain Fab to prevent wrong pairing of light chains. XGFR was produced with high expression yields and showed simultaneous binding to IGF-1R and EGFR with high affinity. Due to monovalent binding of XGFR to IGF-1R, IGF-1R internalization was strongly reduced compared with the bivalent parental antibody, leading to enhanced Fc-mediated cellular cytotoxicity. To further increase immune effector functions triggered by XGFR, the Fc portion of the bispecific antibody was glycoengineered, which resulted in strong antibody-dependent cell-mediated cytotoxicity activity. XGFR-mediated inhibition of IGF-1R and EGFR phosphorylation as well as A549 tumor cell proliferation was highly effective and was comparable with a combined treatment with EGFR (GA201) and IGF-1R (R1507) antibodies. XGFR also demonstrated potent anti-tumor efficacy in multiple mouse xenograft tumor models with a complete growth inhibition of AsPC1 human pancreatic tumors and improved survival of SCID beige mice carrying A549 human lung tumors compared with treatment with antibodies targeting either IGF-1R or EGFR. In summary, we have applied rational antibody engineering technology to develop a heterodimeric OAscFab-IgG bispecific antibody, which combines potent signaling inhibition with antibody-dependent cell-mediated cytotoxicity induction and results in superior molecular properties over two established tetravalent bispecific formats.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.