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A Humanized Anti–4-1BB Monoclonal Antibody Suppresses Antigen-Induced Humoral Immune Response in Nonhuman Primates

Hong, Hyo J.; Lee, Jae W.*; Park, Sung Sup; Kang, Young Jun; Chang, Sun Young*; Kim, Kwang-Mi*; Kim, Jae-Ouk*; Murthy, Krishna K.; Payne, Jennifer S.; Yoon, Sung Kwan§; Park, Mi-Jeong§; Kim, In-Chull§; Kim, Joong Gon; Kang, Chang-Yuil*

Basic Studies

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.

Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea; Colleges of *Pharmacy and †Medicine, Seoul National University, Seoul, Korea; ‡Southwest Foundation for Biomedical Research, San Antonio, Texas; and §Biotech Research Institute, LG Chemical Ltd., Taejon, Korea

Received January 4, 2000; accepted July 5, 2000.

Address correspondence and reprint requests to Dr. Chang-Yuil Kang, Laboratory of Immunology, College of Pharmacy, Seoul National University, Shillim-Dong, Kwanak-Gu, Seoul 151-742, Korea.

© 2000 Lippincott Williams & Wilkins, Inc.