ArticleScientific reports2023
Rabbit derived VL single-domains as promising scaffolds to generate antibody-drug conjugates.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Beyond amyloid: nanobody-mediated neuroinflammatory therapy for Alzheimer's disease.Translational neurodegeneration · 2025Review
- Overcoming resistant cancerous tumors through combined photodynamic and immunotherapy (photoimmunotherapy).Frontiers in immunology · 2025Review
- A new treatment for canine B-cell lymphoma based on a recombinant single-domain antibody immunotoxin derived fromFrontiers in veterinary science · 2025Article
- Cancer immunotherapy and its facilitation by nanomedicine.Biomarker research · 2024Review
- Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies?Marine drugs · 2023Review
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not found in the human or mouse. Thus, to develop a new generation of ADCs, we explored the potential of rabbit-derived VL-single-domain antibody scaffolds (sdAbs) to selectively conjugate a payload to Cys80. Hence, a rabbit sdAb library directed towards canine non-Hodgkin lymphoma (cNHL) was subjected to in vitro and in vivo phage display. This allowed the identification of several highly specific VL-sdAbs, including C5, which specifically target cNHL cells in vitro and present promising in vivo tumor uptake. C5 was selected for SN-38 site-selective payload conjugation through its exposed free Cys80 to generate a stable and homogenous C5-DAB-SN-38. C5-DAB-SN-38 exhibited potent cytotoxicity activity against cNHL cells while inhibiting DNA-TopoI activity. Overall, our strategy validates a platform to develop a novel class of ADCs that combines the benefits of rabbit VL-sdAb scaffolds and the canine lymphoma model as a powerful framework for clinically translation of novel therapeutics for cancer.
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