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| 1 | CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells显示文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19. | Ke Wang Wei Chen Zheng Zhang Yongqiang Deng Jian-Qi Lian Peng Du Ding Wei Yang Zhang Xiu-Xuan Sun Li Gong Xu Yang Lei He Lei Zhang Zhiwei Yang Jie-Jie Geng Ruo Chen Hai Zhang Bin Wang Yu-Meng Zhu Gang Nan Jian-Li Jiang Ling Li Jiao Wu Peng Lin Wan Huang Liangzhi Xie Zhao-Hui Zheng Kui Zhang Jin-Lin Miao Hong-Yong Cui Min Huang Jun Zhang Ling Fu Xiang-Min Yang Zhongpeng Zhao Shihui Sun Hongjing Gu Zhe Wang Chun-Fu Wang Yacheng Lu Ying-Ying Liu Qing-Yi Wang Huijie Bian Ping Zhu Zhi-Nan Chen | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 9 |
| 2 | Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin's lymphoma显示文摘Objective: This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody(SCT400) in Chinese patients with CD20-positive B-cell nonHodgkin's lymphoma(CD20+ B-cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians.Methods: Fifteen patients with CD20+ B-cell NHL received dose-escalating SCT400 infusions(250 mg/m^2: n=3; 375 mg/m^2: n=9; 500 mg/m^2: n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses.Results: No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer(NK) cell count or immunoglobulin levels. No patient developed antiSCT400 antibodies during the course of the study. SCT400 serum half-life(T1/2), maximum concentration(Cmax) and area under the curve(AUC) generally increased between the first and fourth infusions(P<0.05). At the 375 mg/m^2 dose, the T1/2 was 122.5±46.7 h vs. 197.0±75.0 h, respectively, and the Cmax was 200.6±20.2 μg/m L vs. 339.1±71.0 μg/m L, respectively. From 250 mg/m^2 to 500 mg/m^2, the Cmax and AUC increased significantly in a dose-dependent manner(P<0.05). Patients with a high tumor burden had markedly lower serum SCT400 concentrations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses.Conclusions: SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20+ B-cell NHL. | Lin Gui Xiaohong Han Xiaohui He Yuanyuan Song Jiarui Yao Jianliang Yang Peng Liu Yan Qin Shuxiang Zhang Weijing Zhang Wenlin Gai Liangzhi Xie Yuankai Shi | 2016 | Chinese Journal of Cancer Research2016，28，2： | 5 |
| 3 | Double lock of a potent human therapeutic monoclonal antibody against SARS-CoV-2显示文摘Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2.Halting these steps can cure COVID-19.Here we have identified and characterized a potent human monoclonal antibody,HB27,that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations.Remarkably,HB27 can also prevent SARS-CoV-2 membrane fusion.Consequently,a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models.Rhesus macaques showed no obvious adverse events when administrated with10 times the effective dose of HB27.Cryo-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 receptor.Binding of the antibody also restrains any further conformational changes of the receptor binding domain,possibly interfering with progression from the prefusion to the postfusion stage.These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19. | 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 | 2021 | National Science Review2021，8，3： | 3 |
| 4 | Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathy via regulating macrophage heterogeneity显示文摘Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance.The therapeutic effect of stem cell derived-small extracellular vesicles(sEVs)for tendinopathy has been validated in recent years.However,whether large extracellular vesicles(lEVs),another subset of extracellular vesicles,possesses the ability for the improvement of tendinopathy remains unknown.Here,we showed that lEVs secreted from iPSC-derived MSCs(iMSC-lEVs)significantly mitigated pain derived from tendinopathy in rats.Immuno-histochemical analysis showed that iMSC-lEVs regulated the heterogeneity of infiltrated macrophages and several inflammatory cytokines in rat tendon tissue.Meanwhile,in vitro experiments revealed that the M1 pro-inflammatory macrophages were repolarized towards M2 anti-inflammatory macrophages by iMSC-lEVs,and this effect was mediated by regulating p38 MAPK pathway.Moreover,liquid chromatography-tandem mass spectrometry analysis identified 2208 proteins encapsulated in iMSC-lEVs,including 134 new-found proteins beyond current Vesiclepedia database.By bioinformatics and Western blot analyses,we showed that DUSP2 and DUSP3,the negative regulator of p38 phosphorylation,were enriched in iMSC-lEVs and could be transported to macrophages.Further,the immunomodulatory effect of iMSC-lEVs on macrophages was validated in explant tendon tissue from tendinopathy patients.Taken together,our results demonstrate that iMSC-lEVs could reduce inflammation in tendinopathy by regulating macrophage heterogeneity,which is mediated via the p38 MAPK pathway by delivery of DUSP2 and DUSP3,and might be a promising candidate for tendinopathy therapy. | Teng Ye Zhengsheng Chen Jieyuan Zhang Lei Luo Renzhi Gao Liangzhi Gong Yuhang Du Zongping Xie Bizeng Zhao Qing Li Yang Wang | 2023 | Bioactive Materials2023，，3： | 2 |
| 5 | Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma显示文摘Objective:The mainstay treatment of esophageal squamous cell carcinoma(ESCC)involves chemotherapy and immunotherapy.However,alternative therapies are required for patients who are refractory or intolerant to existing therapies.Methods:In this single-arm,multicenter,open-label phase Ib study,30 patients received an intravenous infusion of SCT200,an antiepidermal growth factor receptor(EGFR)monoclonal antibody,6.0 mg/kg once a week for 6 weeks,followed by 8.0 mg/kg once every 2 weeks until disease progression or intolerable toxicity.The primary endpoint was the objective response rate(ORR).The secondary endpoints were progression-free survival(PFS),overall survival(OS),and safety.Results:Thirty patients were enrolled between July 2018 and May 2019.The ORR was 16.7%(95%CI:5.6%–34.7%).The median PFS and OS were 3.1 months(95%CI:1.5–4.3)and 6.8 months(95%CI:4.7–10.1),respectively.A numerical difference without any statistical significance in ORR was observed in patients with different EGFR expressions(≥50%:25.0%vs.<50%:0%,P=0.140)or TP53 mutation abundance(<10%:23.8%vs.≥10%:0%,P=0.286).Improved median PFS(3.4 vs.1.4 months,P=0.006)and OS(8.0 vs.4.2 months,P=0.027)were associated with TP53 mutation abundance of<10%.The most common treatment-related adverse events of grade 3 or 4(occurring in≥2 patients)were hypomagnesemia[7(23.3%)]and rash[2(6.7%)].No treatmentrelated death occurred.Conclusions:SCT200 monotherapy as the second-or further-line treatment for advanced ESCC showed favorable efficacy,with an acceptable safety profile.TP53 mutation abundance might serve as a potential predictive biomarker. | Ming Bai Meng Wang Ting Deng Yuxian Bai Kai Zang Zhanhui Miao Wenlin Gai Liangzhi Xie Yi Ba | 2022 | Cancer Biology & Medicine2022，19，3： | 2 |
| 6 | Quantification of SARS-CoV-2 antigen levels in the blood of patients with COVID-19显示文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused the global outbreak of coronavirus disease 2019(COVID-19).By far,more than 35 million people had been infected by SARS-CoV-2,resulting in more than 1 million deaths globally.It is well recognized that SARSCoV-2 preferentially attacks pulmonary epithelial cells,leading to acute respiratory distress syndrome(ARDS). | Bin Su Jiming Yin Xingguang Lin Tiantian Zhang Xiao Yao Ying Xu Yao Lu Wenzhi Wang Kun Liu Jie Zhang Liangzhi Xie Ronghua Jin Yingmei Feng | 2021 | Science China(Life Sciences)2021，64，7： | 2 |
| 7 | A multi-center,open-label,randomized,parallel-controlled phase II study comparing pharmacokinetic,pharmacodynamics and safety of ripertamab(SCT400)to rituximab(Mab Thera?)in patients with CD20-positive B-cell non-Hodgkin lymphoma显示文摘Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL. | Xiaohong Han Mingzhi Zhang Huaqing Wang Qingyuan Zhang Wei Li Miaowang Hao Yuhuan Gao Jie Jin Hanyun Ren Yun Tang Xiaonan Hong Xiaoyan Ke Hang Su Lin Gui Jianmin Luo Liangzhi Xie Wenlin Gai Yuankai Shi | 2022 | Chinese Journal of Cancer Research2022，34，6： | 1 |
| 8 | A spike-trimer protein-based tetravalent COVID-19 vaccine elicits enhanced breadth of neutralization against SARS-CoV-2 Omicron subvariants and other variants显示文摘Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-Co V-2 variants.In this study,we developed a tetravalent COVID-19 vaccine SCTV01E,based on the trimeric Spike protein of SARS-Co V-2 variants Alpha,Beta,Delta,and Omicron BA.1,with a squalenebased oil-in-water adjuvant SCT-VA02B.In the immunogenicity studies in na?ve BALB/c and C57BL/6J mice,SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-Omicron variants(D614G,Alpha,Beta,and Delta)and newly emerging Omicron subvariants(BA.1,BA.1.1,BA.2,BA.3,and BA.4/5).Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against Omicron subvariants,compared with the D614G booster regimen.Furthermore,SCTV01E vaccination elicited na?ve and central memory T cell responses to SARS-Co V-2 ancestral strain and Omicron spike peptides.Together,our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 variants.SCTV01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and m RNA vaccines(NCT05323461). | Rui Wang Hongpeng Huang Chulin Yu Chunyun Sun Juan Ma Desheng Kong Yalong Lin Dandan Zhao Shaozheng Zhou Jianbo Lu Sai Cao Yanjing Zhang Chunxia Luo Xuefeng Li Yang Wang Liangzhi Xie | 2023 | Science China(Life Sciences)2023，66，8： | 1 |
| 9 | An antibody cocktail with broadened mutational resistance and effective protection against SARS-CoV-2显示文摘Neutralizing antibodies have been proven to be highly effective in treating mild and moderate COVID-19 patients,but continuous emergence of SARS-CoV-2 variants poses significant challenges.Antibody cocktail treatments reduce the risk of escape mutants and resistance.In this study,a new cocktail composed of two highly potent neutralizing antibodies(HB27 and H89Y)was developed,whose binding epitope is different from those cocktails that received emergency use authorization.This cocktail showed more potent and balanced neutralizing activities(IC_(50)0.9–11.3 ng mL^(-1))against a broad spectrum of SARS-CoV-2 variants over individual HB27 or H89Y antibodies.Furthermore,the cocktail conferred more effective protection against the SARS-CoV-2 Beta variant in an aged murine model than monotherapy.It was shown to prevent SARS-CoV-2 mutational escape in vitro and effectively neutralize 61 types of pseudoviruses harbouring single amino acid mutation originated from variants and escape strains of Bamlanivimab,Casirivimab and Imdevimab with IC_(50)of 0.6–65 ng mL^(-1).Despite its breadth of variant neutralization,the HB27+H89Y combo and EUA cocktails lost their potencies against Omicron variant.Our results provide important insights that new antibody cocktails covering different epitopes are valuable tools to counter virus mutation and escape,highlighting the need to search for more conserved epitopes to combat Omicron. | Chunyun Sun Hang Chi Fei Yuan Jing Li Ji Yang Aihua Zheng Fei Wang Lingling Sun Yanjing Zhang Ping Hu Lihua Jiao Yongqiang Deng Liangzhi Xie | 2023 | Science China(Life Sciences)2023，66，1： | 0 |
| 10 | Mutation N856K in spike reduces fusogenicity and infectivity of Omicron BA.1显示文摘Dear Editor,COVID-19 lung pathology is characterized by interstitial pneumonia with cell-cell fusion-induced syncytia and extensive tissue damage.1 The correlation between viral fusogenicity and pathogenicity has been reported in SARS-CoV-2 variants.2 Compared with the previous Delta or D614G variants,Omicron BA.1 has been proven to be less fusogenic and pathogenic. | Chunyun Sun Huiyu Wang Ji Yang Desheng Kong Yuning Chen Haiyue Wang Lingling Sun Jianbo Lu Min Teng Liangzhi Xie | 2023 | Signal Transduction and Targeted Therapy2023，8，3： | 0 |
| 11 | CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells显示文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19. | Ke Wang Wei Chen Zheng Zhang Yongqiang Deng Jian-Qi Lian Peng Du Ding Wei Yang Zhang Xiu-Xuan Sun Li Gong Xu Yang Lei He Lei Zhang Zhiwei Yang Jie-Jie Geng Ruo Chen Hai Zhang Bin Wang Yu-Meng Zhu Gang Nan Jian-Li Jiang Ling Li Jiao Wu Peng Lin Wan Huang Liangzhi Xie Zhao-Hui Zheng Kui Zhang Jin-Lin Miao Hong-Yong Cui Min Huang Jun Zhang Ling Fu Xiang-Min Yang Zhongpeng Zhao Shihui Sun Hongjing Gu Zhe Wang Chun-Fu Wang Yacheng Lu Ying-Ying Liu Qing-Yi Wang Huijie Bian Ping ZhuZhi-Nan Chen | 2021 | Signal Transduction and Targeted Therapy2021，6，1： | 0 |
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