Humanization of an antibody directed against IgE.
IgE antibodies bind to specific high-affinity receptors on mast cells, leading to mast cell degranulation and release of mediators, such as histamine, which produce symptoms associated with allergy. Hence, anti-IgE antibodies that block binding of IgE to its high-affinity receptor are of potential therapeutic value in the treatment of allergy. These antibodies must also not bind to IgE once it is bound to the receptor because this would trigger histamine release. This study describes the humanization of a murine antibody, MaE11, with these characteristics. Variants of the humanized antibody were evaluated to probe the importance of framework residues on antibody binding and to determine which charged residues in the CDR interacted with IgE. We found that only five changes in human framework residues were required to provide for binding comparable to that of the original murine antibody.
Presta
L G
LG
Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.
Lahr
S J
SJ
Shields
R L
RL
Porter
J P
JP
Gorman
C M
CM
Fendly
B M
BM
Jardieu
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017455:Receptors, IgE / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; C026408:anti-IgE antibodies; D007073:Immunoglobulin E