Generation and characterization of CD1d-specific single-domain antibodies with distinct functional features.
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.
Department of Medical Oncology, VU University Medical Centre, Amsterdam, the Netherlands.
Roeland
R
Lameris
Department of Medical Oncology, VU University Medical Centre, Amsterdam, the Netherlands.
Renée C G
RC
de Bruin
Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Paul M P
PM
van Bergen En Henegouwen
Department of Medical Oncology, VU University Medical Centre, Amsterdam, the Netherlands.
Henk M
HM
Verheul
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands.
Sonja
S
Zweegman
Department of Medical Oncology, VU University Medical Centre, Amsterdam, the Netherlands.
Tanja D
TD
de Gruijl
Department of Medical Oncology, VU University Medical Centre, Amsterdam, the Netherlands.
Hans J
HJ
van der Vliet
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000494:pharmacology*; D017951:Antigen Presentation; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D002161:Camelids, New World; D002454:Cell Differentiation; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D055611:Natural Killer T-Cells / Q000276:immunology*; D019151:Peptide Library; D057127:Single-Chain Antibodies / Q000235:genetics; D061905:Single-Domain Antibodies / Q000235:genetics
D000911:Antibodies, Monoclonal; D055610:Antigens, CD1d; D019151:Peptide Library; D057127:Single-Chain Antibodies; D061905:Single-Domain Antibodies
CD1d; cancer; dendritic cell; invariant natural killer T-cell; variable domain of heavy-chain-only antibody