Antibody engineering of a cytotoxic monoclonal antibody 84 against human embryonic stem cells: Investigating the effects of multivalency on cytotoxicity

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• 作者：Maximilian Klement^a ; ^b ; Jiyun Zheng^a ; ^c ; Chengcheng Liu^a ; Heng-Liang Tan^a ; Victor Vai Tak Wong^a ; Andre Boon-Hwa Choo^a ; ^d ; Dong-Yup Lee^a ; ^b ; ^e ; ^{cheld@nus.edu.sg} ; Dave Siak-Wei Ow^a ; ^{dave_ow@bti.a-star.edu.sg} ; ^{dave_ow@yahoo.com}
• 关键词：BSA ; bovine serum albumine ; EB ; embryoid body ; Fab ; fragment antigen binding ; hESC ; human embryonic stem cells ; HPLC ; high-pressure liquid chromatograpy ; HRP ; horseradish peroxidase ; IgG ; immunoglobulin G ; IgM ; immunoglobulin M ; IPTG ; isopropyl β -d-1-thiogalactopyranoside ; mAb ; monoclonal antibody ; PEG ; polyethylene glycol ; PODXL-1 ; podocalaxin like protein-1 ; scFv ; single chain fragment variable ; SEC ; size-exclusion chromatography ; ZIP ; GCN4 Leucine Zipper
• 刊名：Journal of Biotechnology
• 出版年：2017
• 出版时间：10 February 2017
• 年：2017
• 卷：243
• 期：Complete
• 页码：29-37
• 全文大小：1816 K
• 卷排序：243

文摘

Engineered cytotoxic scFv fragments against hESC with a valency from one to four were constructed. We hypothesized that higher cytotoxicity would be observed for fragments with increased valency. Trimeric and tetrameric engineered fragments were more cytotoxic to undifferentiated hESC. Engineered fragments showed improved tissue penetration into cell clusters over parental IgM. Implications for antibody-mediated removal of undifferentiated hESC during stem cell therapy.