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Double lock of a potent human therapeutic monoclonal antibody against SARS-CoV-2

National Science Review 2021年第3期8卷 29-41页

作者： Ling Zhu Yong-Qiang Deng Rong-Rong Zhang Zhen Cui Chun-Yun Sun Chang-Fa Fan Xiaorui Xing Weijin Huang Qi Chen Na-Na Zhang Qing Ye Tian-Shu Cao Nan Wang Lei Wang Lei Cao Huiyu Wang Desheng Kong Juan Ma Chunxia Luo Yanjing Zhang Jianhui Nie Yao Sun Zhe Lv Neil Shaw Qianqian Li Xiao-Feng Li Junjie Hu Liangzhi Xie Zihe Rao Youchun Wang Xiangxi Wang Cheng-Feng Qin CAS Key Laboratory of Infection and Immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of Sciences State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAcademy of Military Medical Sciences Beijing Engineering Research Center of Protein and Antibody Sinocelltech Ltd. Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC) School of Basic Medical Sciences Southwest Medical University Division of HIV/AIDS and Sex-Transmitted Virus Vaccines Institute for Biological Product Control NIFDC Beijing Key Laboratory of Monoclonal Antibody Research and Development Sino Biological Inc. Cell Culture Engineering Center Chinese Academy of Medical Sciences &Peking Union Medical College Guangzhou Regenerative Medicine and Health Guangdong Laboratory

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by *** these steps can cure *** we have identified and characterized a potent human monoclonal antibody,HB27,that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM ***,HB27 can also prevent SARS-CoV-2 membrane ***,a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse *** macaques showed no obvious adverse events when administrated with10 times the effective dose of ***-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to the ACE2 *** of the antibody also restrains any further conformational changes of the receptor binding domain,possibly interfering with progression from the prefusion to the postfusion *** results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.

关键词： SARS-CoV-2 COVID-19 in vivo protection preclinical safety evaluation human neutralizing antibody immuno-therapy cryo-EM structure

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PD-1/PD-L1 checkpoint blockade in immune-antitumortherapy：advances and perspectives

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中国药理学与毒理学杂志 2017年第10期31卷 963-963页

作者： Yu LI Ji JIANG Bei HU Peking Union Medical College Hospital Beijing 100032 China

During the past three decades,studies have shown that tumor cells could"manipulate"host immunity to escape the immune defenses in the tumor *** of the most important underlying mechanisms is immune-suppression regulated by programmed cell death-1 or its ligand 1(PD-1/PD-L1),which makes PD-1/PD-L1 blockadea promising target of cancer *** could suppress immuno-response of T cells by activating PD-1/PD-L1 signaling ***,inhibiting the interaction between PD-1 and PD-L1 could reconstitute the enduring antitumor immunity in the tumor microenvironment via enhancing the T-cell response,there after augmenting the endogenous antitumor force of the immune *** these lines,inhibitors of PD-1/PD-L1 has been applied in multiple clinical trials against various types of *** studies indicated that PD-1/PD-L1 blockade have demonstrated high efficacy and safety against melanoma,lung,kidney and several other solid tumors,as well as hematological ***,the efficacy of this checkpoint blockade approach is not *** investigation suggested that lack of responses to anti-PD-1/PD-L1 therapy of patients without PD-1/PD-L1 over-expression was *** this review,we summarize the history and current understanding of multiple intrinsic and extrinsic mechanisms via which PD-1/PD-L1 is regulated and research advances in preclinical/clinical aspects of PD-1/PD-L1,as well as significance and perspectives regarding the PD-1/PD-L1 blockade in immune-antitumor therapy.

关键词： PD-1 PD-L1 checkpoint blockade immuno-therapy research advaces

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