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MeSH: CD40 Antigens-immunology

4 záznamů v Medvik Filtry

Článek

Inhibition of CD40L with Frexalimab in Multiple Sclerosis

Vermersch, Patrick
Autor Vermersch, Patrick From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Granziera, Cristina
Autor Granziera, Cristina From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Mao-Draayer, Yang
Autor Mao-Draayer, Yang From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Cutter, Gary
Autor Cutter, Gary From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Kalbus, Oleksandr
Autor Kalbus, Oleksandr From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Staikov, Ivan
Autor Staikov, Ivan From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Dufek, Michal
Autor Dufek, Michal From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Saubadu, Stephane
Autor Saubadu, Stephane From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Bejuit, Raphael
Autor Bejuit, Raphael From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)
Truffinet, Philippe
Autor Truffinet, Philippe From the University of Lille, INSERM Unité 1172, Lille Neuroscience and Cognition, Lille University Hospital, University Hospital Federation Precise, Lille (P.V.), and Sanofi, Chilly-Mazarin (S.S., R.B., P.T.) - both in France Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, and the Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel and University of Basel, Basel, Switzerland (C.G.) the Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, Ann Arbor, and the Michigan Institute for Neurological Disorders, Farmington Hills (Y.M.-D.) the Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham (G.C.) the Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine (O.K.) the Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.) the First Department of Neurology, St. Anne's University Hospital, Brno, Czech Republic (M.D.) Sanofi, Cambridge, MA (B.D., E.W.) and Queen Mary University of London, London (G.G.)

The New England journal of medicine. 2024 ; 390 (7) : 589-600. [pub] 20240215

N Engl J Med
ISSN 1533-4406
Medvik
Zdroj

BACKGROUND: The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis. METHODS: In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab. RESULTS: Of 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% confidence interval [CI], 0.1 to 0.4) in the group that received 1200 mg of frexalimab intravenously and 0.3 (95% CI, 0.1 to 0.6) in the group that received 300 mg of frexalimab subcutaneously, as compared with 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios as compared with placebo were 0.11 (95% CI, 0.03 to 0.38) in the 1200-mg group and 0.21 (95% CI, 0.08 to 0.56) in the 300-mg group. Results for the secondary imaging end points were generally in the same direction as those for the primary analysis. The most common adverse events were coronavirus disease 2019 and headaches. CONCLUSIONS: In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628.).

Článek

Mannan-BAM, TLR Ligands, Anti-CD40 Antibody (MBTA) Vaccine Immunotherapy: A Review of Current Evidence and Applications in Glioblastoma

International journal of molecular sciences. 2021 ; 22 (7) : . [pub] 20210326

Int J Mol Sci
ISSN 1422-0067
Medvik
Zdroj

The foundation of precision immunotherapy in oncology is rooted in computational biology and patient-derived sample sequencing to enrich for and target immunogenic epitopes. Discovery of these tumor-specific epitopes through tumor sequencing has revolutionized patient outcomes in many types of cancers that were previously untreatable. However, these therapeutic successes are far from universal, especially with cancers that carry high intratumoral heterogeneity such as glioblastoma (GBM). Herein, we present the technical aspects of Mannan-BAM, TLR Ligands, Anti-CD40 Antibody (MBTA) vaccine immunotherapy, an investigational therapeutic that potentially circumvents the need for in silico tumor-neoantigen enrichment. We then review the most promising GBM vaccination strategies to contextualize the MBTA vaccine. By reviewing current evidence using translational tumor models supporting MBTA vaccination, we evaluate the underlying principles that validate its clinical applicability. Finally, we showcase the translational potential of MBTA vaccination as a potential immunotherapy in GBM, along with established surgical and immunologic cancer treatment paradigms.

Článek

Cilostazol suppresses LPS-stimulated maturation of DC2.4 cells through inhibition of NF-κB pathway

Journal of Applied Biomedicine. 2012 ; 10 (4) : 177-186.

J. Appl. Biomed. (Čes. Budějovice Print)
ISSN 1214-021X
Medvik
Zdroj

Cilostazol is a phosphodiesterase-3 inhibitor that functions as a platelet aggregation inhibitor and is used for treating peripheral artery diseases and ischemic stroke. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. Cilostazol has anti-atherogenic and anti-inflammatory effects, but the effects of cilostazol on DC maturation remain unknown. The purpose of this study was to determine the effects of cilostazol on lipopolysaccharide (LPS)-induced maturation of DCs. DC2.4 cells were treated with cilostazol for 12 h and subsequently stimulated with LPS to induce maturation. Cilostazol reduced the expression of maturation-associated markers induced by LPS, such as CD40, CD86, and MHCII, improved the endocytotic function, and decreased production of the tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) of these cells. To further elucidate the mechanisms responsible for the inhibition of DC2.4 maturation by cilostazol, we investigated the effect of cilostazol on LPS-stimulated nuclear factor-kappa B (NF-κB) activation. Our results indicated that cilostazol treatment decreased IκBα degradation and inhibited NF-κB p65 translocation, and the inhibitory effects of cilostazol were cAMP-independent. Therefore, inhibition of NF-κB by cilostazol might result in the suppression of DC maturation. In conclusion, cilostazol suppressed LPS-stimulated DC maturation, which might contribute to its anti-atherosclerosis effect.

Článek

Tick saliva inhibits dendritic cell migration, maturation, and function while promoting development of Th2 responses

The Journal of immunology. 2008 ; 180 (9) : 6186-6192.

J Immunol
ISSN 0022-1767
Medvik
Zdroj

Similarly to other blood-feeding arthropods, ticks have evolved immunosuppressive mechanisms enabling them to overcome the host immune system. Although the immunomodulatory effect of tick saliva on several cell populations of the immune system has been extensively studied, little is known about its impact on dendritic cells (DCs). We have examined the effect of Ixodes ricinus tick saliva on DC function in vitro and in vivo. Exposure of DCs to tick saliva in vitro resulted in impaired maturation, upon CD40 or TLR9, TLR3 and TLR7 ligation, as well as reduced Ag presentation capacity. Administration of tick saliva in vivo significantly inhibited maturation and early migration of DCs from inflamed skin to draining lymph nodes, and decreased the capacity of lymph node DCs to present soluble Ag to specific T cells. Moreover, saliva-exposed DCs failed to induce efficient Th1 and Th17 polarization and promoted development of Th2 responses. Our data reveal a complex inhibitory effect exerted by tick saliva on DC function. Given the role of DCs as the key instigators of adaptive immune responses, alteration of their function might represent a major mechanism of tick-mediated immune evasion.

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