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Journal of Cancer Therapy 2012年第4期3卷 269-277页

作者： Andreas Nechansky Stefan Stranner Oliver Scheiber Nicole Halanek Ralf Kircheis apeiron biologics ag Igeneon GmbH Vienna Austria Virologik GmbH Erlangen Germany

Purpose: Detailed analysis of a patient with epithelial Lewis Y (LeY) positive cancer who received twice 50 mg of the humanized Lewis Y carbohydrate specific mAb IGN311 and developed a clinically significant human anti-human antibody (HAHA) response (Ab2). Results: Clinical stabilization of the disease was assigned to in this patient. The HAHA response consisted mainly of IgG1 and was found to be directed against the IGN311 binding site. Consistent with the induction of the HAHA response, CDC activity against Lewis Y positive target cells was completely abolished at day 8 and could not be restored by the second 50 mg infusion indicating complete neutralization of applied IGN311. The ADCC reactivity was also significantly reduced and anti-anti idiotype-specific antibodies (Ab3) were detectable at day 65. Conclusions: Induction of Ab3 antibodies should be considered as an additional factor influencing the efficacy of humanized antibodies. In this context, the potential threat of induced HAHA responses against therapeutic mAbs might have to be reconsidered because they might actually have also beneficial immunological long-term effects leading to an active immunization component induced by therapeutic antibodies.

关键词： Lewis Y Carbohydrate Immunotherapy Immunogenicity Anti-Idiotype HAHA (Human Anti-Human Antibodies)

Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders

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World Journal of Diabetes 2022年第6期13卷 434-441页

作者： Arjun Jain Kristof Bozovicar Vidhi Mehrotra Tomaz Bratkovic Martin H Johnson Ira Jha ET-Traps Limited Cambridge CB30JEUnited Kingdom Department of Physiology Development and NeuroscienceUniversity of CambridgeCambridge CB23DYUnited Kingdom Accelerate Cambridge Judge Business SchoolUniversity of CambridgeCambridge CB21AGUnited Kingdom Department of Pharmaceutical Biology Faculty of PharmacyUniversity of LjubljanaSlovenia 1000Slovenia

BACKGROUND Endothelin(ET)-traps are Fc-fusion proteins with a design based on the physiological receptors of *** work has shown that use of the selected ET-traps potently and significantly reduces different markers of diabetes pathology back to normal,non-disease *** To demonstrate the selected ET-traps potently and significantly bind to *** We performed phage display experiments to test different constructs of ET-traps,and conducted bio-layer interferometry binding assays to verify that the selected ET-traps bind specifically to ET-1 and display binding affinity in the double-digit picomolar range(an average of 73.8 rM,n=6).RESULTS These experiments have confirmed our choice of the final ET-traps and provided proof-of-concept for the potential use of constructs as effective biologics for diseases associated with pathologically elevated *** There is increased need for such therapeutics as they could help save millions of lives around the world.

关键词： Endothelin-1 Endothelin-traps Diabetes Heart failure Chronic kidney disease Novel therapeutic

The metabolite BH4 controls T cell proliferation in autoimmunity and cancer

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四川生理科学杂志 2023年第10期45卷 1825-1825页

作者： Shane J F Cronin IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences Vienna Austria. Department of Neurobiology Harvard Medical School Boston MA USA. FM Kirby Neurobiology Center Boston Children's Hospital Boston MA USA. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology AUVA Research Center Vienna Austria. Département de Pharmacologie et Physiologie Université de Montréal Montréal Québec Canada. Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-University Mainz Mainz Germany. Department of Internal Medicine II (Infectious Diseases Immunology Rheumatology and Pneumology) Medical University of Innsbruck Innsbruck Austria. Institute of Chemical Sciences and Engineering Institute of Bioengineering National Centre of Competence in Research (NCCR) in Chemical Biology École Polytechnique Fédérale de Lausanne (EPFL) Lausanne Switzerland. Division of Cardiovascular Medicine British Heart Foundation Centre for Research Excellence John Radcliffe Hospital University of Oxford Oxford UK. Wellcome Trust Centre for Human Genetics Roosevelt Drive University of Oxford Oxford UK. Division of Gastroenterology and Liver Center Department of Medicine Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) Harvard University Boston MA USA. LABOX Departamento de Bioquímica Universidade Federal de Santa Catarina Florianópolis Brazil. Research Institute of Molecular Pathology Vienna Biocenter Campus-Vienna-Biocenter 1 Vienna Austria. Karolinska Institute Department of Medicine Solna Center for Molecular Medicine Karolinska University Hospital Solna Stockholm Sweden. Department of Neuronal Control of Metabolism Max Planck Institute for Metabolism Research Cologne Germany. Department of Neurosciences Centre de Recherche de CHU de Québec-Université Laval Québec Québec Canada. Department of Molecular Medicine Faculty of Medicine Université Laval Québec Quebec Canada. Neurosurgery Departm

Genetic regulators and environmental stimuli modulate T cell activation in autoimmunity and *** enzyme co-factor tetrahydrobiopterin(BH4)is involved in the production of monoamine neurotransmitters,the generation of n... 详细信息

关键词： BH4 cancer. autoimmunity

Secukinumab provided significant and sustained improvement in the signs and symptoms of ankylosing spondylitis:results from the 52-week,PhaseⅢChina-centric study,MEASURE 5

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Chinese Medical Journal 2020年第21期133卷 2521-2531页

作者： Feng Huang Fei Sun Wei-Guo Wan Li-Jun Wu Ling-Li Dong Xiao Zhang Tae-Hwan Kim Raj Sengupta Ladislav Senolt Yi Wang Hao-Min Qiu Brian Porter Sibylle Haemmerle Department of Rheumatology Chinese People’s Liberation Army General HospitalBeijing 100853China Department of Rheumatology Huashan HospitalFudan UniversityShanghai 200040China Department of Rheumatology&Immunology People's Hospital of Xinjiang Uygur Autonomous RegionUrumqiXinjiang 830001China Department of Rheumatology&Immunology Tongji HospitalTongji Medical College of Huazhong University of Science&TechnologyWuhanHubei 430030China Department of Rheumatology&Immunology Guangdong General HospitalGuangzhouGuangdong 510000China Hanyang University Hospital for Rheumatic Diseases SeoulRepublic of Korea Royal National Hospital for Rheumatic Disease Upper Borough WallsBath BA11RLUK Institute of Rheumatology PragueCzech Republic Novartis Pharmaceuticals Corporation East HanoverNJUSA China Novartis Institutes for Biomedical Research Shanghai 201203China Novartis Pharma ag BaselSwitzerland

Background:Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis(AS)through 5 years in pivotal Phase III ***,we present efficacy and safety results(52-week)of secukinumab in patients with AS from the MEASURE 5 ***:MEASURE 5 was a 52-week,Phase III,China-centric *** patients were randomly assigned(2:1)to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks(q4w).All placebo patients switched to secukinumab 150 mg q4w starting at Week *** endpoint was Assessments of SpondyloArthritis international Society(ASAS)20 at Week *** was stratified by region(China ***-China).Results:Of 458 patients(secukinumab 150 mg,N=305;placebo,N=153)randomized,327(71.4%)were from China and 131(28.6%)were not from *** these,97.7%and 97.4%patients completed Week 16 and 91.1%and 95.3%(placebo-secukinumab)patients completed Week 52 of *** primary endpoint was met;secukinumab significantly improved ASAS20 response at Week 16 ***(58.4%vs.36.6%;P<0.0001);corresponding rate in the Chinese population was 56.0%vs.38.5%(P<0.01).All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16;responses were maintained with a trend toward increased efficacy from Week 16 to *** new or unexpected safety signals were reported up to Week ***:Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of *** was well tolerated and the safety profile was consistent with previous *** and safety results were comparable between the overall and Chinese populations.

关键词： Ankylosing spondylitis biologics Cytokines Interleukin 17A Tumor necrosis factor

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19

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四川生理科学杂志 2021年第1期43卷 94-94页

作者： Michael J Joyner From the Departments of Anesthesiology and Perioperative Medicine (M.J.J. J.W.S. S.A.K. C.C.W. A.M.K. M.A.S. J.C.D.S. S.E.B. J.R.A.S. V.H. A.J.C. J.G.R. K.J.A. M.N.P.V. J.J.D. R.J.R.) Laboratory Medicine and Pathology (J.R.M. E.S.T. C.M.B. J.L.W. J.R.S.) and Cardiovascular Medicine (R.F.R. K.F.L. R.S.W.) the Human Research Protection Program (R.S.W.) and the Department of Internal Medicine Division of Pulmonary and Critical Care Medicine (P.R.B.) Mayo Clinic Rochester MN the Departments of Health Sciences Research (R.E.C. P.W.J. E.R.L. D.O.H.) and Cardiovascular Medicine (K.A.B. E.R.W. D.F.) Mayo Clinic Jacksonville FL the Department of Health Sciences Research (K.L.K. M.R.B.) and the Department of Internal Medicine Division of Infectious Diseases (J.E.B.) Mayo Clinic Phoenix AZ the Department of Anesthesiology Cooper Medical School of Rowan University Cooper University Health Care Camden NJ (N.H.) the Center for biologics Evaluation and Research Food and Drug Administration Silver Spring (N.C.V. P.M.) and the Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Baltimore (A.C.) — both in Maryland and the Departments of Epidemiology and Biostatistics and of Pediatrics and Human Development College of Human Medicine Michigan State University East Lansing (N.S.P.).

Background:Convalescent plasma has been widely used to treat coronavirus disease 2019(Covid-19)under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)that can be passively transferred to the plasma *** convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is ***:In a retrospective study based on a *** registry,we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19.

关键词： Plasma transferred retrospective