An anti-EGFR × cotinine bispecific antibody complexed with cotinine-conjugated duocarmycin inhibits growth of EGFR-positive cancer cells with KRAS mutations

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作者
Junyeong Jin
Gunwoo Park
Jong Bae Park
Soohyun Kim
Hyori Kim
Junho Chung
机构
[1] Seoul National University College of Medicine,Department of Biochemistry and Molecular Biology
[2] Seoul National University College of Medicine,Department of Biomedical Science
[3] Seoul National University College of Medicine,Cancer Research Institute
[4] National Cancer Center,Research Institute
[5] Graduate School of Cancer Science and Policy,Department of Cancer Biomedical Science, National Cancer Center
[6] National Cancer Center,Research Institute
[7] Asan Medical Center,Asan Institute for Life Sciences
来源
Experimental & Molecular Medicine | 2018年 / 50卷
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摘要
Antibody-drug conjugates (ADCs) can selectively deliver cytotoxic agents to tumor cells and are frequently more potent than naked antibodies. However, optimization of the conjugation process between antibodies and cytotoxic agents and characterization of ADCs are laborious and time-consuming processes. Here, we describe a novel ADC platform using a tetravalent bispecific antibody that simultaneously binds to the tumor-associated antigen and a hapten conjugated to a cytotoxic agent. We selected cotinine as the hapten because it is not present in biological systems and is inert and nontoxic. We prepared an anti-epidermal growth factor receptor (EGFR) × cotinine bispecific antibody and mixed it with an equimolar amount of cotinine-conjugated duocarmycin to form the ADC. This ADC showed significant in vitro and in vivo antitumor activity against EGFR-positive, cetuximab-refractory lung adenocarcinoma cells with KRAS mutations.
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页码:1 / 14
页数:13
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