Humanization of mouse anti-human IL-2 receptor antibody B-B10.
Mouse monoclonal anti-human IL-2 receptor antibody (B-B10) inhibits IL-2-dependent human T-cell proliferation. It has been used in clinical trials in the transplantation field and promising results are being accumulated. Mouse B-B10 antibody was humanized by grafting all CDRs and some framework amino acid residues onto human antibodies, KAS for VH and PAY for V kappa. Nine humanized B-B10s with differently grafted framework residues were constructed and assessed for their biological activities. One of these humanized B-B10, M5, showed nearly the same activity as the mouse B-B10. The 49th residue of V kappa was demonstrated to play a crucial role in the antigen-antibody interaction by 3-D structure analysis with a computer modeling system.
Nakatani
T
T
Sumitomo Chemical Co., Ltd, Biotechnology Laboratory, Takarazuka Research Center, Hyogo, Japan.
Lone
Y C
YC
Yamakawa
J
J
Kanaoka
M
M
Gomi
H
H
Wijdenes
J
J
Noguchi
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D003001:Cloning, Molecular; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005818:Genetic Engineering; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D017385:Sequence Homology; D013329:Structure-Activity Relationship; D014162:Transfection
D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D015375:Receptors, Interleukin-2; D004247:DNA