Functional characterization of N297A, a murine surrogate for low-Fc binding anti-human CD3 antibodies.
Several low- or non-FcR binding anti-human CD3 monoclonal antibodies have been under investigation for the treatment of autoimmune diseases. To model the mechanism of action of these anti-human CD3 mAbs in the murine system, an Fc-modified anti-mouse CD3 antibody (N297A) was generated. N297A exhibited similar biological effects as Fc-modified anti-human CD3 antibodies including rapid, reversible reduction in peripheral leukocyte numbers, differential modulation of activated versus resting T cells, and reduced levels of induced cytokine release compared to the non-Fc-modified parent antibody. In an in vivo model of colitis induced by adoptive transfer of IL-10-deficient cells, administration of N297A significantly reduced body weight loss. As N297A shared many functional characteristics of non-FcR binding anti-human CD3 mAbs both in vitro and in vivo, it provides a means to model the mechanisms of action of Fc-modified anti-human CD3 antibodies in mouse.
Chao
Debra T
DT
Research Department, PDL BioPharma, Redwood City, California 94063, USA. Debra.chao@pdl.com
Ma
Xiaohong
X
Li
Olga
O
Park
Hyunjoo
H
Law
Debbie
D
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D003092:Colitis / Q000276:immunology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011485:Protein Binding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin