Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation.
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.
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.|Co-operative Research Centre for Biomarker Translation, Melbourne, Victoria, Australia.
T A
TA
Seldon
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.
R
R
Pryor
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.
A
A
Palkova
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
M L
ML
Jones
Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
N D
ND
Verma
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.
M
M
Findova
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.
K
K
Braet
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.|Co-operative Research Centre for Biomarker Translation, Melbourne, Victoria, Australia.
Y
Y
Sheng
Anesthesia, Helen Diller Family Comprehensive Cancer Centre, University of California, San Francisco, CA, USA.
Y
Y
Fan
Anesthesia, Helen Diller Family Comprehensive Cancer Centre, University of California, San Francisco, CA, USA.
E Y
EY
Zhou
Anesthesia, Helen Diller Family Comprehensive Cancer Centre, University of California, San Francisco, CA, USA.
J D
JD
Marks
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
T
T
Munro
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
S M
SM
Mahler
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
R T
RT
Barnard
Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
P D
PD
Fromm
Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
P A
PA
Silveira
Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
Z
Z
Elgundi
Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
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X
Ju
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.|Co-operative Research Centre for Biomarker Translation, Melbourne, Victoria, Australia.|Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
G J
GJ
Clark
Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
K F
KF
Bradstock
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.|Co-operative Research Centre for Biomarker Translation, Melbourne, Victoria, Australia.
D J
DJ
Munster
DC Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.|Co-operative Research Centre for Biomarker Translation, Melbourne, Victoria, Australia.|Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.|Dendritic Cell Research, ANZAC Research Institute, Concord, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
D N J
DN
Hart
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D000097802:CD83 Antigen
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen