Amelioration of murine immune thrombocytopenia by CD44 antibodies: a potential therapy for ITP?
To explore the potential for monoclonal antibodies as a treatment for immune thrombocytopenia (ITP) and to further explore their mechanisms of action, we tested 8 monoclonal CD44 antibodies in murine ITP and found 4 antibodies that could successfully ameliorate ITP; 2 of these antibodies function at a full 3-log fold lower dosage compared with IVIg. Further characterization of the 2 most successful antibodies (5035-41.1D and KM114) demonstrated that, similar to IVIg: (1) the presence of the inhibitory IgG receptor FcγRIIB was required for their ameliorative function, (2) complement-deficient mice responded to anti-CD44 treatment, and (3) human transgenic FcγRIIA-expressing mice also responded to the CD44 therapeutic modality. Dissimilar to IVIg, the Fc portion of the CD44 antibody was not required. These data demonstrate that CD44 antibodies can function therapeutically in murine ITP and that they could potentially provide a very-low-dose recombinant therapy for the amelioration of human ITP.
Canadian Blood Services, Toronto, ON, Canada.
Andrew R
AR
Crow
Seng
S
Song
Sara J
SJ
Suppa
Shuhua
S
Ma
Michael P
MP
Reilly
Pierrette
P
Andre
Steven E
SE
McKenzie
Alan H
AH
Lazarus
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D003176:Complement C3; C080568:Fc gamma receptor IIA; C499172:Fcgr2b protein, mouse; D018960:Hyaluronan Receptors; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG