Toxicity of major histocompatibility complex class II specific monoclonal antibodies: audietur et altera pars.
OBJECTIVE
To investigate whether in vivo toxicity of class II major histocompatibility complex (MHC) specific monoclonal antibodies (mAb) is contributed by mAb's constant region binding to Fc receptor (FcR).


METHODS
Laboratory mice were injected intravenously (i.v.) with class II MHC-specific mAb of various isotypes and respective antigen-binding fragments, and their clinical status was observed subsequently.


RESULTS
All anti-class II mAb of the IgG2a isotype exhibit acute toxicity, manifested in severe lethargy and a frequent death. No adverse effects were observed after the FcR-binding capability of the toxic mAb was eliminated via deletion or mutation of its Fc segment.


CONCLUSIONS
In vivo toxicity of anti-class II mAb appears to be the consequence of the crosslinking of class II+ cells with cells expressing FcR.
Dendreon Corporation, 3005 1st Avenue, Seattle, WA 98121, USA. dvidovic@dendreon.com
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001666:Binding Sites, Antibody / Q000235:genetics / Q000276:immunology; D002423:Cause of Death; D005260:Female; D017353:Gene Deletion; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000008:administration & dosage / Q000276:immunology; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D011961:Receptors, Fc / Q000276:immunology*; D012894:Sleep Stages / Q000276:immunology
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011961:Receptors, Fc