1. Generation and characterization of CD1d-specific single-domain antibodies with distinct functional features.
- Author
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Lameris R, de Bruin RC, van Bergen En Henegouwen PM, Verheul HM, Zweegman S, de Gruijl TD, and van der Vliet HJ
- Subjects
- Animals, Antibodies, Monoclonal genetics, Antigen Presentation, Antigens, CD1d immunology, Apoptosis, Camelids, New World, Cell Differentiation, Cell Line, Humans, Multiple Myeloma immunology, Peptide Library, Single-Chain Antibodies genetics, Single-Domain Antibodies genetics, Antibodies, Monoclonal pharmacology, Antigens, CD1d metabolism, B-Lymphocytes immunology, Dendritic Cells immunology, Immunotherapy methods, Multiple Myeloma therapy, Natural Killer T-Cells immunology
- Abstract
Ligation of the CD1d antigen-presenting molecule by monoclonal antibodies (mAbs) can trigger important biological functions. For therapeutic purposes camelid-derived variable domain of heavy-chain-only antibodies (VHH) have multiple advantages over mAbs because they are small, stable and have low immunogenicity. Here, we generated 21 human CD1d-specific VHH by immunizing Lama glama and subsequent phage display. Two clones induced maturation of dendritic cells, one clone induced early apoptosis in CD1d-expressing B lymphoblasts and multiple myeloma cells, and another clone blocked recognition of glycolipid-loaded CD1d by CD1d-restricted invariant natural killer T (iNKT) cells. In contrast to reported CD1d-specific mAbs, these CD1d-specific VHH have the unique characteristic that they induce specific and well-defined biological effects. This feature, combined with the above-indicated general advantages of VHH, make the CD1d-specific VHH generated here unique and useful tools to exploit both CD1d ligation as well as disruption of CD1d-iNKT interactions in the treatment of cancer or inflammatory disorders., (© 2016 John Wiley & Sons Ltd.)
- Published
- 2016
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