Format

Send to

Choose Destination
Leukemia. 2016 Mar;30(3):692-700. doi: 10.1038/leu.2015.231. Epub 2015 Aug 19.

Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation.

Author information

1
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.
2
Co-operative Research Centre for Biomarker Translation, Melbourne, Victoria, Australia.
3
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
4
Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.
5
University of Sydney, Sydney, New South Wales, Australia.
6
Anesthesia, Helen Diller Family Comprehensive Cancer Centre, University of California, San Francisco, CA, USA.
7
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.

Abstract

Current immunosuppressive/anti-inflammatory agents target the responding effector arm of the immune response and their nonspecific action increases the risk of infection and malignancy. These effects impact on their use in allogeneic haematopoietic cell transplantation and other forms of transplantation. Interventions that target activated dendritic cells (DCs) have the potential to suppress the induction of undesired immune responses (for example, graft versus host disease (GVHD) or transplant rejection) and to leave protective T-cell immune responses intact (for example, cytomegalovirus (CMV) immunity). We developed a human IgG1 monoclonal antibody (mAb), 3C12, specific for CD83, which is expressed on activated but not resting DC. The 3C12 mAb and an affinity improved version, 3C12C, depleted CD83(+) cells by CD16(+) NK cell-mediated antibody-dependent cellular cytotoxicity, and inhibited allogeneic T-cell proliferation in vitro. A single dose of 3C12C prevented human peripheral blood mononuclear cell-induced acute GVHD in SCID mouse recipients. The mAb 3C12C depleted CMRF-44(+)CD83(bright) activated DC but spared CD83(dim/-) DC in vivo. It reduced human T-cell activation in vivo and maintained the proportion of CD4(+) FoxP3(+) CD25(+) Treg cells and also viral-specific CD8(+) T cells. The anti-CD83 mAb, 3C12C, merits further evaluation as a new immunosuppressive agent in transplantation.

PMID:
26286117
DOI:
10.1038/leu.2015.231
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center