A humanized anti--4-1BB monoclonal antibody suppresses antigen-induced humoral immune response in nonhuman primates

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Title
A humanized anti--4-1BB monoclonal antibody suppresses antigen-induced humoral immune response in nonhuman primates
Author(s)
Hyo Jeong Hong; Jae W Lee; Sung Sup Park; Young Jun Kang; Sun Young Chang; Kwang Mi Kim; Jae Ouk Kim; Krishna K Murthy; Jennifer S Payne; Sung Kwan Yoon; Mi Jeong Park; In Chull Kim; Joong Gon Kim; Chang Yuil Kang
Bibliographic Citation
Journal of Immunotherapy, vol. 23, no. 6, pp. 613-621
Publication Year
2000
Abstract
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.
Keyword
Autoimmune diseaseHumanized anti-4-1BB monoclonal antibodyImmunosuppressionImmunotherapyNonhuman primate
ISSN
1053-8550
Publisher
Kluwer
DOI
http://dx.doi.org/10.1097/00002371-200011000-00002
Type
Article
Appears in Collections:
Division of Research on National Challenges > Aging Research Center > 1. Journal Articles
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