1. Humanization of agonistic anti-human 4-1BB monoclonal antibody using a phage-displayed combinatorial library
- Author
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Son, Ji Hee, Lee, Unn Hwa, Lee, Jeong Jin, Kwon, Byungsuk, Kwon, Byoung Se, and Park, Jeong Woo
- Subjects
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T cells , *MONOCLONAL antibodies , *ANTIGENS , *BLOOD cells - Abstract
Given the key role 4-1BB plays in the stimulation of T cells, humanization of agonistic anti-human 4-1BB monoclonal antibody (mAb) may have important clinical applications. In this paper, we present the humanization of agonistic anti-human 4-1BB mAb, BBK-4, using a phage display library. We first prepared the combinatorial library by incorporating murine and human alternative at positions representing buried residues that might affect the structural integrity of the antigen binding site. Six humanized single chain Fv (scFv) fragments were selected from the combinatorial library expressing phage-displayed humanized scFv. They were found to retain the epitope specificity of the original mAb but had affinities of lower than 1/10 of the original. In spite of the lower affinity, the humanized scFv coated on the surface expanded human peripheral blood mononuclear cells (PBMCs) in MLR similarly to the original mAb in the presence of anti-CD3 mAb. These results suggest that humanized anti-human 4-1BB scFvs can be used as a valuable reagent for clinical application. [Copyright &y& Elsevier]
- Published
- 2004
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