Journal
IMMUNOLOGY
Volume 149, Issue 1, Pages 111-121Publisher
WILEY
DOI: 10.1111/imm.12635
Keywords
cancer; CD1d; dendritic cell; invariant natural killer T-cell; variable domain of heavy-chain-only antibody
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Funding
- CCA-VICI grant from the VU University Medical Centre [2000483]
- Dutch Cancer Society (KWF) [VU 2010-4728]
- Worldwide Cancer Research [14-0343]
- Worldwide Cancer Research [14-0343] Funding Source: researchfish
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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.
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