A humanized anti--4-1BB monoclonal antibody suppresses antigen-induced humoral immune response in nonhuman primates.
The interaction of 4-1BB and its ligand plays an important role in the regulation of T-cell-mediated immune responses. In this study, the authors examined the effect of a humanized anti--4-1BB monoclonal antibody (H4B4) on ovalbumin-induced immune responses in baboons. Previously, a mouse monoclonal antibody, 4B4 against the human 4-1BB molecule, was generated and characterized. Based on this antibody, a humanized version of 4B4 monoclonal antibody was constructed and the resultant antibody, H4B4, showed full recovery of the binding activity of the original antibody 4B4: a 1.5-fold increase in affinity for 4-1BB. In addition, H4B4 mediated antibody-dependent cellular cytotoxicity of activated human peripheral blood T cells and CEM cells in a dose-dependent manner. Weekly administration of H4B4 at doses of 1 or 4 mg/kg could suppress immunoglobulin G production against ovalbumin. This was not a result of the overall immune suppression, because the numbers of B and T cells and the total immunoglobulin G production were not altered during treatment with H4B4. These findings suggest that treatment with H4B4 may be a valid therapeutic approach to control unwanted immune responses in persons with autoimmune diseases.
Hong
H J
HJ
Korea Research Institute of Bioscience and Biotechnology, Taejon.
Lee
J W
JW
Park
S S
SS
Kang
Y J
YJ
Chang
S Y
SY
Kim
K M
KM
Kim
J O
JO
Murthy
K K
KK
Payne
J S
JS
Yoon
S K
SK
Park
M J
MJ
Kim
I C
IC
Kim
J G
JG
Kang
C Y
CY
D053330:4-1BB Ligand; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000941:Antigens / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016131:Lymphocyte Subsets / Q000166:cytology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010047:Ovalbumin / Q000276:immunology; D010215:Papio; D011994:Recombinant Proteins / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D000941:Antigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; C505974:TNFSF9 protein, human; C505975:Tnfsf9 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin