一种HER2双特异性抗体可以在[具体表达体系]中高效表达，并具有强大的细胞毒性。 （注：原文中“in with”表述有误，推测可能是“in [具体表达体系]”，这里按推测补充完整翻译）
A HER2 bispecific antibody can be efficiently expressed in with potent cytotoxicity.
作者信息
Lin Limin, Li Li, Zhou Changhua, Li Jing, Liu Jiayu, Shu Rui, Dong Bin, Li Qing, Wang Zhong
机构信息
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, P.R. China.
Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, Guangdong 510006, P.R. China.
出版信息
Oncol Lett. 2018 Jul;16(1):1259-1266. doi: 10.3892/ol.2018.8698. Epub 2018 May 11.
Abstract
Bispecific antibodies have been actively studied for cancer therapy due to their potent cytotoxicity against tumor cells. A number of bispecific antibody formats have exhibited strong tumor cytotoxicity and . However, effective production of bispecific antibodies remains challenging for the majority of bispecific antibody formats. In the present study, a bispecific antibody was designed that links a conventional antigen-binding fragment (Fab) against cluster of differentiation 3 antigen (CD3) to a camel single domain antibody (VHH) against human epidermal growth factor receptor 2 (HER2). This bispecific antibody may be secreted and purified efficiently from culture medium. The purified bispecific antibody is able to trigger T cell-mediated HER2-specific cytotoxicity and . The data gathered in the present study suggest that this bispecific format may be applied to other tumor antigens to produce bispecific antibodies more efficiently.
摘要
由于双特异性抗体对肿瘤细胞具有强大的细胞毒性，因此已被积极研究用于癌症治疗。许多双特异性抗体形式已表现出强大的肿瘤细胞毒性。然而，对于大多数双特异性抗体形式而言，有效生产双特异性抗体仍然具有挑战性。在本研究中，设计了一种双特异性抗体，它将针对分化簇3抗原（CD3）的传统抗原结合片段（Fab）与针对人表皮生长因子受体2（HER2）的骆驼单域抗体（VHH）连接起来。这种双特异性抗体可以从培养基中高效分泌和纯化。纯化后的双特异性抗体能够触发T细胞介导的HER2特异性细胞毒性。本研究收集的数据表明，这种双特异性形式可应用于其他肿瘤抗原，以更有效地生产双特异性抗体。
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本文引用的文献
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Am J Cancer Res. 2016 Nov 1;6(11):2661-2678. eCollection 2016.
2
Adjuvant trastuzumab: a 10-year overview of its benefit.辅助性曲妥珠单抗：其疗效的十年综述
Expert Rev Anticancer Ther. 2017 Jan;17(1):61-74. doi: 10.1080/14737140.2017.1264876. Epub 2016 Dec 5.
3
Effects of lapatinib or trastuzumab, alone and in combination, in human epidermal growth factor receptor 2-positive breast cancer: a meta-analysis of randomized controlled trials.拉帕替尼或曲妥珠单抗单药及联合用药对人表皮生长因子受体2阳性乳腺癌的影响：一项随机对照试验的荟萃分析
Cancer Med. 2016 Dec;5(12):3454-3463. doi: 10.1002/cam4.963. Epub 2016 Nov 23.
4
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BMC Cancer. 2016 Jul 7;16:420. doi: 10.1186/s12885-016-2449-0.
5
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AMB Express. 2016 Dec;6(1):32. doi: 10.1186/s13568-016-0201-4. Epub 2016 Apr 26.
6
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7
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PLoS One. 2015 Dec 17;10(12):e0144712. doi: 10.1371/journal.pone.0144712. eCollection 2015.
8
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9
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