Failed efficacy of soluble human CD83-Ig in allogeneic mixed lymphocyte reactions and experimental autoimmune encephalomyelitis: implications for a lack of therapeutic potential.
Soluble forms of CD83, a dendritic cell-specific surface glycoprotein, have been strongly proposed to be of therapeutic utility in inflammatory conditions such as multiple sclerosis and transplantation. We demonstrate here, however, that eukaryotically expressed, recombinant soluble human CD83-Ig molecules fail to achieve efficacy in model systems for those conditions: mouse experimental autoimmune encephalomyelitis models in vivo or in mixed lymphocyte reactions in vitro. These results raise concern as to the viability of a eukaryotically expressed soluble CD83 strategy for clinical therapeutic use.
Pashine
Achal
A
Roche Palo Alto, LLC, Palo Alto, CA 94304, USA.
Göpfert
Ulrich
U
Chen
Jinzhi
J
Hoffmann
Eike
E
Dietrich
Paul S
PS
Peng
Stanford L
SL
D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D000097802:CD83 Antigen
D015703:Antigens, CD; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D000097802:CD83 Antigen