ArticlemAbs2017
Humanization of rabbit monoclonal antibodies via grafting combined Kabat/IMGT/Paratome complementarity-determining regions: Rationale and examples.
Article in mAbs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- Preclinical development of mesothelin-targeting CAR T cells for the treatment of cholangiocarcinoma.Hepatology communications · 2026Article
- RO4, a high-affinity humanized antibody against the juxtamembrane region of mesothelin for targeted cancer therapy.Antibody therapeutics · 2026Article
- Cross-reactive sarbecovirus antibodies induced by mosaic RBD nanoparticles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles.bioRxiv : the preprint server for biology · 2025Article
- Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.The American journal of pathology · 2025Review
- Antibody numbering schemes: advances, comparisons and tools for antibody engineering.Protein engineering, design & selection : PEDS · 2025Review
- Newly developed humanized anti-CKAP4 antibody suppresses pancreatic cancer growth by inhibiting DKK1-CKAP4 signaling.Cancer science · 2024Article
- Cancer therapy with antibodies.Nature reviews. Cancer · 2024Review
- Computational Protein Design - Where it goes?Current medicinal chemistry · 2024Review
- SARS-CoV-2 Spike Protein Interaction Space.International journal of molecular sciences · 2023Article
- A mammalian cell display platform based on scFab transposition.Antibody therapeutics · 2023Article
- A highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer.Journal for immunotherapy of cancer · 2023Article
- A novel humanized Chi3l1 blocking antibody attenuates acetaminophen-induced liver injury in mice.Antibody therapeutics · 2023Article
- Humanization of the Shark VCurrent protocols · 2023Article
- Evaluation of chimeric antigen receptor of humanized rabbit-derived T cell receptor-like antibody.Cancer science · 2022Article
- Development of Highly Effective Anti-Mesothelin hYP218 Chimeric Antigen Receptor T Cells With Increased Tumor Infiltration and Persistence for Treating Solid Tumors.Molecular cancer therapeutics · 2022Article
- Somatic Hypermutation and Framework Mutations of Variable Region Contribute to Anti-Zika Virus-Specific Monoclonal Antibody Binding and Function.Journal of virology · 2022Article
- Therapeutic effects of TM4SF5-targeting chimeric and humanized monoclonal antibodies in hepatocellular and colon cancer models.Molecular therapy oncolytics · 2022Article
- Article
- Optimization of anti-ADAMTS13 antibodies for the treatment of ADAMTS13-related bleeding disorder in patients receiving circulatory assist device support.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Rabbit monoclonal antibodies (RabMAbs) can recognize diverse epitopes, including those poorly immunogenic in mice and humans. However, there have been only a few reports on RabMAb humanization, an important antibody engineering step usually done before clinical applications are investigated. To pursue a general method for humanization of RabMAbs, we analyzed the complex structures of 5 RabMAbs with their antigens currently available in the Protein Data Bank, and identified antigen-contacting residues on the rabbit Fv within the 6 Angstrom distance to its antigen. We also analyzed the supporting residues for antigen-contacting residues on the same heavy or light chain. We identified "HV4" and "LV4" in rabbit Fvs, non-complementarity-determining region (CDR) loops that are structurally close to the antigen and located in framework 3 of the heavy chain and light chain, respectively. Based on our structural and sequence analysis, we designed a humanization strategy by grafting the combined Kabat/IMGT/Paratome CDRs, which cover most antigen-contacting residues, into a human germline framework sequence. Using this strategy, we humanized 4 RabMAbs that recognize poorly immunogenic epitopes in the cancer target mesothelin. Three of the 4 humanized rabbit Fvs have similar or improved functional binding affinity for mesothelin-expressing cells. Interestingly, 4 immunotoxins composed of the humanized scFvs fused to a clinically used fragment of Pseudomonas exotoxin (PE38) showed stronger cytotoxicity against tumor cells than the immunotoxins derived from their original rabbit scFvs. Our data suggest that grafting the combined Kabat/IMGT/Paratome CDRs to a stable human germline framework can be a general approach to humanize RabMAbs.
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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.