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Title 

Guided selection of human antibody light chain against TAG-72 using a phage display chain shuffling approach

Authors 

Sang Jick KimHyo Jeong Hong

Publisher 

Microbiological Society of Korea

Issue Date 

2007

Citation 

Journal of Microbiology, vol. 45, no. 6, pp. 572-577

Keywords 

chain shufflingguided selectionmonoclonal antibodyphage displayTAG-72immunoglobulin F(ab) fragmentpeptide librarytumor antigentumor associated antigen 72

Abstract 

To enhance therapeutic potential of murine monoclonal antibody, humanization by CDR grafting is usually used to reduce immunogenic mouse residues. Most humanized antibodies still have mouse residues critical for antigen binding, but the mouse residues may evoke immune responses in humans. Previously, we constructed a new humanized version (AKA) of mouse CC49 antibody specific for tumor-associated glycoprotein, TAG-72. In this study, to select a completely human antibody light chain against TAG-72, guided selection strategy using phage display was used. The heavy chain variable region (VH) of AKA was used to guide the selection of a human TAG-72-specific light chain variable region (VL) from a human VL repertoire constructed from human PBL. Most of the selected VLs were identified to be originated from the members of the human germline VK1 family, whereas the VL of AKA is more homologous to the VK4 family. Competition binding assay of the selected Fabs with mouse CC49 suggested that the epitopes of the Fabs overlap with that of CC49. In addition, they showed better antigen-binding affinity compared to parental AKA. The selected human VLs may be used to guide the selection of human VHs to get completely human anti-TAG72 antibody.

ISSN 

1225-8873

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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