ArticleFrontiers in immunology2021
Grabbing the Bull by Both Horns: Bovine Ultralong CDR-H3 Paratopes Enable Engineering of 'Almost Natural' Common Light Chain Bispecific Antibodies Suitable For Effector Cell Redirection.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Therapeutic efficacy of bovine ultra-long CDR H3 antibody against BVDV in challenged BALB/c mouse model.Frontiers in immunology · 2026Article
- The characterization of variable new antigen receptors targeting FAP isolated from a novel immunized library.Communications biology · 2025Article
- Bovine Ultra-Long CDR H3 Specific for Bovine Rotavirus Displays Potent Virus Neutralization and Therapeutic Effects in Infected Calves.Biomolecules · 2025Article
- Stability convergence in natural antibodies with ultra-long hypervariable loops.Communications biology · 2025Article
- Enhancing NK cell-mediated tumor killing of B7-H6Molecular therapy. Oncology · 2025Article
- Development of FAP-targeted theranostics discovered by next-generation sequencing-augmented mining of a novel immunized VNAR library.bioRxiv : the preprint server for biology · 2025Article
- Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire.PLoS pathogens · 2024Article
- Estimates of Sequences with Ultralong and Short CDR3s in the Bovine IgM B Cell Receptor Repertoire Using the Long-read Oxford Nanopore MinION Platform.ImmunoHorizons · 2024Article
- The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies.Acta crystallographica. Section F, Structural biology communications · 2024Article
- HIV envelope trimers and gp120 as immunogens to induce broadly neutralizing antibodies in cows.bioRxiv : the preprint server for biology · 2024Article
- Modular design of bi- and multi-specific knob domain fusions.Frontiers in immunology · 2024Article
- NKp46-specific single domain antibodies enable facile engineering of various potent NK cell engager formats.Protein science : a publication of the Protein Society · 2023Article
- Cattle-derived knob paratopes grafted onto peripheral loops of the IgG1 Fc region enable the generation of a novel symmetric bispecific antibody format.Frontiers in immunology · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A subset of antibodies found in cattle comprises ultralong CDR-H3 regions of up to 70 amino acids. Interestingly, this type of immunoglobulin usually pairs with the single germline VL gene, V30 that is typically very conserved in sequence. In this work, we have engineered ultralong CDR-H3 common light chain bispecific antibodies targeting Epidermal Growth Factor Receptor (EGFR) on tumor cells as well as Natural Cytotoxicity Receptor NKp30 on Natural Killer (NK) cells. Antigen-specific common light chain antibodies were isolated by yeast surface display by means of pairing CDR-H3 diversities following immunization with a single V30 light chain. After selection, EGFR-targeting paratopes as well as NKp30-specific binders were combined into common light chain bispecific antibodies by exploiting the strand-exchange engineered domain (SEED) technology for heavy chain heterodimerization. Biochemical characterization of resulting bispecifics revealed highly specific binding to the respective antigens as well as simultaneous binding to both targets. Most importantly, engineered cattle-derived bispecific common light chain molecules elicited potent NK cell redirection and consequently tumor cell lysis of EGFR-overexpressing cells as well as robust release of proinflammatory cytokine interferon-γ. Taken together, this data is giving clear evidence that bovine bispecific ultralong CDR-H3 common light chain antibodies are versatile for biotechnological applications.
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