A5035574878- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Asthma and respiratory diseases
- CAR-T cell therapy research
- Dermatology and Skin Diseases
- Psoriasis: Treatment and Pathogenesis
- Helicobacter pylori-related gastroenterology studies
- Immune Cell Function and Interaction
- Hidradenitis Suppurativa and Treatments
- NF-κB Signaling Pathways
- Whipple's Disease and Interleukins
- Urticaria and Related Conditions
- Mast cells and histamine
- Microscopic Colitis
- HIV Research and Treatment
- Immune Response and Inflammation
- Pediatric health and respiratory diseases
- Colorectal and Anal Carcinomas
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Antimicrobial Peptides and Activities
- Estrogen and related hormone effects
- Food Allergy and Anaphylaxis Research
- Autoimmune and Inflammatory Disorders
Novartis (Switzerland)
2017-2025
Novartis Institutes for BioMedical Research
2021-2023
Vita-Salute San Raffaele University
2012
Roche (Switzerland)
2004-2007
Union Bank of Switzerland
2006
Zero to Three
2005
University of Tübingen
2001
Interleukin 17 is a T cell-derived cytokine that induces the release of pro-inflammatory mediators in wide range cell types. Recently, subset IL-17-producing helper cells (Th17) distinct from Th1 and Th2 has been described, which constitutes new polarization state. Aberrant Th17 responses overexpression IL-17 have implicated number autoimmune disorders including rheumatoid arthritis multiple sclerosis. Molecules blocking such as IL-17-specific monoclonal antibodies proved to be effective...
The most common reason for heart failure in young adults is dilated cardiomyopathy often resulting from myocarditis. Clinical studies and animal models provide evidence that an autoimmune response against myosin the underlying disease. IL-12 has been suggested to play a key role development of experimental myocarditis (EAM), as IL-12p40 IL-12Rbeta1 knockouts are protected In this study, we have compared IL-12p40-/- mice, IL-12p35-/- mice treated with neutralizing IL-23 antibody EAM found...
Interleukin-36 receptor (IL-36R), belonging to the IL-1 family, is crucial for host defense and tissue repair. Targeting cytokine receptors with low molecular weight (LMW) compounds remains challenging due their interaction large surface area of cytokine. In this study, two encoded library technologies are used identify LMW molecules binding IL-36R's extracellular domain. The mRNA-based display technique identifies 36R-P138, a macrocyclic peptide blocking IL-36R signaling. Importantly, its...
Leukotriene C4 synthase (LTC4S) is a glutathione S-transferase that mediates the biosynthesis of cysteinyl leukotriene (LTC4). Cysteinyl leukotrienes (CysLTs) are lipid mediators drive type 2 inflammation, bronchoconstriction, and itch. Thus, LTC4S represents an attractive drug target for treatment allergic inflammatory diseases, but to date, no inhibitor has been tested in patients. Herein, we disclose discovery preclinical profiling highly selective, oral GJG057 (compound 1), which...
The cytosolic metalloenzyme leukotriene A
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in substantial impact on patients' QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify high prevalence IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine...
Leukotriene A4 Hydrolase (LTA4H) is a bifunctional zinc metalloenzyme that comprises both epoxide hydrolase and aminopeptidase activity, exerted by two overlapping catalytic sites. The function of the enzyme catalyzes biosynthesis pro-inflammatory lipid mediator leukotriene (LT) B4. Recent literature suggests LTA4H responsible for degradation tripeptide Pro-Gly-Pro (PGP) which neutrophil chemotactic activity has been postulated. It speculated design selective inhibitors spare pocket may...
Chronic pain resulting from inflammatory and neuropathic disorders causes considerable economic social burden. For a substantial proportion of patients, conventional drug treatments do not provide adequate relief. Consequently, novel approaches to management, involving alternative targets new therapeutic modalities compatible with chronic use, are being sought. Nerve growth factor (NGF) is major mediator pain. Clinical testing NGF antagonists ongoing, clinical proof concept has been...
LYS006 is a novel, highly potent and selective, new-generation leukotriene A4 hydrolase (LTA4H) inhibitor in clinical development for the treatment of neutrophil-driven inflammatory diseases. We describe complex pharmacokinetic to pharmacodynamic (PD) relationship blood, plasma, skin LYS006-treated nonclinical species healthy human participants. In randomized first study, participants were exposed single ascending doses up 100 mg multiple 80 b.i.d.. showed rapid absorption, overall dose...
Monoclonal antibodies (mAbs) inhibiting cytokines have recently emerged as new drug modalities for the treatment of chronic inflammatory diseases. Interleukin-17 (IL-17) is a T-cell-derived central mediator autoimmunity. Immunization with Qβ-IL-17, virus-like particle based vaccine, has been shown to produce autoantibodies in mice and was effective ameliorating disease symptoms animal models To characterize induced by vaccination at molecular level, we generated mouse mAbs specific IL-17...
Abstract CD4+ helper T cells play a critical role in orchestrating host immune responses, including antitumor immunity. The limited availability of MHC class II–associated tumor antigens is still viewed as major obstacle the use cancer vaccines. Here, we describe novel approach for identification II tumor-associated (TAAs). By combining two-dimensional liquid chromatography and nanoelectrospray ionization tandem mass spectrometry, developed highly sensitive method detection human leukocyte...
Bacterial capsular polysaccharides are virulence factors and considered T cell-independent antigens. However, the polysaccharide Sp1 from Streptococcus pneumoniae serotype 1 has been shown to activate CD4(+) cells in a major histocompatibility complex (MHC) class II-dependent manner. The mechanism of carbohydrate presentation is unknown. We show live murine dendritic (DCs) that translocates lysosomal compartments plasma membrane MHCII-positive tubules. cell surface results reduction...
Salmonella enterica subspecies 1 serovar Typhimurium (S. Typhimurium) causes diarrhea and acute inflammation of the intestinal mucosa. The pro-inflammatory cytokines IL-17A IL-17F are strongly induced in infected mucosa but their contribution driving tissue is not understood. We have used streptomycin mouse model to analyze role cognate receptor IL-17RA S. enterocolitis. Neutralization did affect mucosal triggered by infection or spread systemic sites 48 h p.i. Similarly, Il17ra−/− mice...
IntroductionLeukotriene A4 hydrolase (LTA4H) is the final and rate limiting enzyme regulating biosynthesis of leukotriene B4 (LTB4), a pro-inflammatory lipid mediator implicated in large number inflammatory pathologies. Inhibition LTA4H not only prevents LTB4 but also induces class-switch within 5-lipoxygenase pathway, elevating anti-inflammatory Lipoxin A4. Ample preclinical evidence advocates as attractive drug target for treatment chronic diseases.Areas coveredThis review covers details...
The discovery of chiral amino alcohols derived from our previously disclosed clinical LTA4H inhibitor LYS006 is described. In a biochemical assay, their optical antipodes showed similar potencies, which could be rationalized by the cocrystal structures these compounds bound to LTA4H. Despite comparable stabilities in liver microsomes, they distinct vivo PK properties. Selective O-phosphorylation (R)-enantiomers blood led clearance values above hepatic flow, whereas (S)-enantiomers were...
Vaccine strategies that target dendritic cells (DC) in order to elicit immunity against tumors are the subject of intense research. For induction and maintenance anti-tumor immunity, CD4+ helper T often required, which need see appropriate MHC class II-peptide complexes on DC. So far, it remained widely unclear what type tumor can feed II processing pathway DC with antigens. Here, we report peptide loading onto molecules myeloid is facilitated by melanoma undergoing necrotic rather than...