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T cells expressing CD5/CD7 bispecific chimeric antigen receptors with fully human heavy-chain-only domains mitigate tumor antigen escape

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1322-1333页

作者： Zhenyu Dai Wei Mu Ya Zhao Jiali Cheng Haolong Lin Kedong Ouyang Xiangyin Jia Jianwei Liu Qiaoe Wei Meng Wang Chaohong Liu Taochao Tan Jianfeng Zhou Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China nanjing iaso biotherapeutics NanjingJiangsu 210000China Department of Pathogen Biology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China

Bispecific chimeric antigen receptor T-cell(CAR-T)therapies have shown promising results in clinical trials for advanced B-cell ***,it is challenging to broaden the success of bispecific CAR-T therapies to treat refractory/relapse(r/r)T-cell leukemia/lymphoma because targeting multiple T-cell-expressing antigens leads to exacerbated CAR-T cell fratricide and potential safety *** human heavy chain variable(FHVH)antibodies that specifically target CD5 or CD7 were screened and constructed to CD5/CD7 bispecific CARs.A truncated Epidermal growth factor receptor were integrated into CAR constructs to address safety *** tackle the fratricidal issue of CAR-T cells targeting T-cell-pan marker(s),CRISPR/Cas9-based CD5 and CD7 genes knockout were performed before lentiviral transduction of bispecific *** comparison between different bispecific CAR structures:tandem CARs and dual CAR were performed in vitro and in vivo to determine the optimal construct suitable for addressing T-cell malignancy antigen escape in clinical *** of CD5 and CD7 prevents fratricide of CD5/CD7 bispecific CAR-T cells,and FHVH-derived CD5/CD7 bispecific CAR-T cells demonstrate potent antitumor activity in vitro and in *** fratricide-resistant FHVH-derived CD5/CD7 bispecific CAR-T cells have potent antitumor activity against T-cell malignancies,and tandem CARs are more effective than dual CAR in preventing tumor escape in heterogeneous leukemic *** meaningful clinical efficacy and safety of tandem CD5/CD7 CAR-T cells deserve to be explored urgently.

关键词： CD7 CRISPR/Cas9 expressing

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Application Effect of Health Management in Community Diabetic Population

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Journal of Biosciences and Medicines 2024年第6期12卷 13-18页

作者： Honglei Wang Siqin Ye School of Management Engineering Wanjiang University of Technology Maanshan China iaso biotherapeutics Nanjing China

Objective: This study aims to improve the health level of patients with diabetes in the community through health management measures under the concept of health management. Methods: Community residents were selected to detect, collate and analyze the social demographic information, body mass index, fasting blood glucose and blood lipid level of diabetic patients before and after health management. Results: The study showed that after the implementation of health management education in the community, the detection rate of diabetes patients increased, but the population was no longer mainly elderly patients, but mainly people under 60 years old. The levels of body mass index, fasting blood glucose, triglyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL) were significantly decreased (all P Conclusion: Through the investigation of patients before and after health management in residential communities, this study shows that the correct implementation of health management can effectively improve the physiological indicators of diabetes patients, improve the level of health quality, and provide a reference for the prevention and treatment of diabetes patients in communities.

关键词： Community Management Diabetes Mellitus Health Education Influencing Factor

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Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders:phase 1 trial interim results

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Signal Transduction and Targeted Therapy 2023年第2期8卷 683-691页

作者： Chuan Qin Dai-Shi Tian Luo-Qi Zhou Ke Shang Liang Huang Ming-Hao Dong Yun-Fan You Jun Xiao Ying Xiong Wen Wang Hao Pang Jing-Jing Guo Song-Bai Cai Di Wang Chun-Rui Li Min Zhang Bi-Tao Bu Wei Wang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina Hubei Key Laboratory of Neural Injury and Functional Reconstruction Huazhong University of Science and Technology430030 WuhanChina Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina nanjing iaso biotherapeutics Ltd NanjingChina

Chimeric antigen receptor(CAR)T-cell therapy that targets B-cell maturation antigen(BCMA)have great potentials in autoimmune diseases and could be novel therapeutics for relapsed/refractory neuromyelitis optica spectrum disorder(NMOSD).To evaluate the safety and efficacy of the CT103A,a self-developed BCMA-targeting CAR construct against BCMA,in patients with AQP4-IgG seropositive NMOSD,an ongoing,investigator-initiated,open-label,single-arm,phase 1 clinical trial is conducted at our *** total,12 patients were administered with a CAR-BCMA *** of the 12 patients dosed were women(83.3%),with a median age of 49.5 years(range,30-67).were The most common events of grade 3 or higher were hematologic toxic *** patients(58%)developed infections,but no grade 4 infections *** release syndrome was reported in all patients with only events of grade 1 or 2 *** the follow-up of a median 5.5 months,11 patients had no relapse;all patients generally reported improvement in disabilities and quality-of-life outcomes;11 patients’AQP-4 antibodies in serum showed a downward trend by the cutoff *** T-cell expansion was associated with responses,and persisted more than 6 months post-infusion in 17%of the *** summary,CAR T-cell therapy shows a manageable safety profile and therapeutic potentials for patients with relapsed/refractory AQP4-IgG seropositive *** expansion phase is currently underway to determine the safety and efficacy of CAR T-BCMA infusion in patients with other neuro-inflammatory diseases.

关键词： AQP4 BCMA infusion

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Triclosan inhibits the activation of human periodontal ligament fibroblasts induced by lipopolysaccharide from Porphyromonas gingivalis

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The Journal of Biomedical Research 2021年第3期35卷 206-215页

作者： Wei Shu Yanman Zhang Chen Zhang Qiang You Hong Zhou Shuang Wen Department of Immunology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China Department of Stomatology Jiangsu Provincial Hospital of Traditional Chinese MedicineNanjingJiangsu 210029China Department of biotherapeutics the Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210011China.

Periodontitis is a highly prevalent,chronic,non-specific,and immunologically devastating disease of periodontal tissues,caused by microbial *** study aims to examine the efficacy and protective mechanism of triclosan(TCS),a bisphenolic,non-cationic component of oral care products,against periodontal inflammation induced by lipopolysaccharide purified from Porphyromonas gingivalis(LPS-PG).TCS markedly downregulated interleukin-6(IL-6),IL-8,and IL-15 in human periodontal ligament fibroblasts(HPDLFs)treated with *** using a liquid chromatography-tandem mass spectrometry(LC-MS/MS)approach,318 differentially expressed proteins(161 upregulated and 157 downregulated)were identified in TCS-pretreated *** upregulated HSPA5 and HSP90B1 but downregulated ***,TCS upregulated miR-548i in HPDLFs,which downregulated *** results indicate that TCS attenuates the activation of HPDLFs and downregulates the inflammatory cytokines through various mechanisms,thus highlighting its protective role in periodontal inflammation.

关键词： human periodontal ligament fibroblasts lipopolysaccharide triclosan heat shock protein

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One-step synthesis of site-specific antibody-drug conjugates by reprograming IgG glycoengineering with LacNAc-based substrates

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2417-2428页

作者： Wei Shi Wanzhen Li Jianxin Zhang Tiehai Li Yakai Song Yue Zeng Qian Dong Zeng Lin Likun Gong Shuquan Fan Feng Tang Wei Huang CAS Key Laboratory of Receptor Research CAS Center for Excellence in Molecular Cell ScienceCenter for Biotherapeutics Discovery ResearchShanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China School of Pharmaceutical Science and Technology Hangzhou Institute of Advanced StudyHangzhou 310024China University of Chinese Academy of Sciences Beijing 100049China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China School of Life Science Liaocheng UniversityLiaocheng 252059China

Glycosite-specific antibody-drug conjugatess(gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation ***, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase(ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type(WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native *** studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

关键词： Site-specific ADCs ENGase LacNAc One-step assembly Potent in vivo efficacy

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ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker

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Signal Transduction and Targeted Therapy 2021年第9期6卷 2897-2905页

作者： Yuning Chen Ya-Nan Zhang Renhong Yan Guifeng Wang Yuanyuan Zhang Zhe-Rui Zhang Yaning Li Jianxia Ou Wendi Chu Zhijuan Liang Yongmei Wang Yi-Li Chen Ganjun Chen Qi Wang Qiang Zhou Bo Zhang Chunhe Wang biotherapeutics Discovery Research Center Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina University of Chinese Academy of Sciences BeijingChina Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhanHubeiChina Center for Infectious Disease Research Westlake Laboratory of Life Sciences and BiomedicineKey Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake Universityand Institute of BiologyWestlake Institute for Advanced StudyHangzhouZhejiangChina Beijing Advanced Innovation Center for Structural Biology Tsinghua-Peking Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijingChina School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjingJiangsuChina Dartsbio Pharmaceuticals ZhongshanGuangdongChina Drug Discovery Center for Infectious Disease Nankai UniversityTianjinChina Fudan University School of PharmacyShanghaiChina

The evolution of coronaviruses,such as SARS-CoV-2,makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought *** we report a human angiotensin-converting enzyme 2(ACE2)-targeting monoclonal antibody,3E8,blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2,SARS-CoV-2 mutant variants(SARS-CoV-2-D614G,B.1.1.7,B.1.351,B.1.617.1,and P.1).

关键词： ACE2 monoclonal prevention

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Living Materials for Life Healthcare

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Accounts of Materials Research 2021年第1期2卷 59-70页

作者： Luoran Shang Changmin Shao Junjie Chi Yuanjin Zhao Zhongshan-Xuhui Hospital The Shanghai Key Laboratory of Medical EpigeneticsInstitutes of Biomedical SciencesFudan UniversityShanghai 200032China Department of Rheumatology and Immunology Institute of Translational MedicineThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Wenzhou Institute University of Chinese Academy of SciencesWenzhouZhejiang 325001China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

CONSPECTUS:Living material is a type of composite material with living elements integrated into nonliving *** combines the advantages of both living cells and nonliving substances and takes advantage of advanced fabrication *** materials is an emerging new paradigm at the frontiers of materials *** addresses an intriguing question of how to let materials show life-like capabilities and function in an integrative and programmable *** all of the capability and application aspects of living materials,the one related to human health is the most intriguing since it implies that that materials could be made by life and used for ***,living materials exploit the merits of cells in that they can respond to environmental variables,synthesize functional molecules,and span multiple length *** the same time,the abundant coordination between live and nonliving elements opens infinite possibilities for diverse structural and functional *** resultant biohybrid materials are thus endowed with novel functions that recapitulate or even surpass their natural candidates and ultimately shed new light on biodiagnostics and biotherapeutics to address human health *** this Account,we present a concise summary and analysis of living materials and bring it into the context of addressing life healthcare *** start with the fabrication of living materials,including the engineering of living elements and the manufacturing of biohybrid composites through advanced technologies,particularly micropatterning,microfluidics,and threedimensional(3D)*** then shift to the properties and capacities of living materials,such as autonomous motion,sensing and actuation,and highly sensitive *** the basis of these,we show,by representative examples,the healthcare-oriented applications of living materials in both diagnostic and biotherapeutic aspects,including biohybrid sensors and actuators,cell-powered robotics,organ

关键词： composites precise Living

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Monoclonal antibody:the corner stone of modern biotherapeutics

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药学学报 2012年第10期47卷 1275-1280页

作者： XIA Zhi-nan CAI Xue-ting CAO Peng R&D Synageva Biopharma Corporation Lexington MA 02421USA Laboratory of Cellular and Molecular Biology Jiangsu Province Institute of Traditional Chinese MedicineNanjing 210028China)

Worldwide sales of biologic drugs exceeded 100 billion USD in *** 32% is from therapeutic monoclonal antibody(mAb).With many blockbuster biopharmaceutical patents expiring over the next decade,there is a great opportunity for biosimilar to enter the worldwide especially emerging *** European Medicines Agency(EMA) and Food and Drug Administration(FDA) have introduced regulatory frameworks for the potential approval of biosimilar mAb *** than providing a highly abbreviated path,as in the case for small molecule chemical drug,approval for biosimilar mAb will require clinical trial and the details will be very much on a case-by-case *** mAb is the dominant category of biologic drugs,mAb will be the focus of this ***,the United States(US) and European Union(EU) approved mAb and those in phase 3 trials will be reviewed,then strategies on how to win biosimilar competition will be reviewed.

关键词： monoclonal antibody biotherapeutic biosimilar biobetter

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