scholarly journals Tumor regression by anti-CD40 and interleukin-2: role of CD40 in hematopoietic cells and organ-specific effects

2004 ◽  
Vol 10 (8) ◽  
pp. 534-539 ◽  
Author(s):  
Lisbeth A. Welniak ◽  
Lynnette Shorts ◽  
Jeff Subleski ◽  
Bruce R. Blazar ◽  
Robert H. Wiltrout ◽  
...  
Keyword(s):  
Tumor Regression ◽  
Interleukin 2 ◽  
Hematopoietic Cells ◽  
Specific Effects ◽  
Organ Specific

Increased Production of Nitric Oxide Mediates Selective Organ-Specific Effects of Endotoxin on Oxidative Stress

2012 ◽  
Vol 11 (2) ◽  
pp. 161-172 ◽  
Author(s):  
Seyhan Sahan-Firat ◽  
Necmiye Canacankatan ◽  
Belma Korkmaz ◽  
Hatice Yildirim ◽  
Lulufer Tamer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Specific Effects ◽  
Organ Specific

scholarly journals A bispecific antibody agonist of the IL-2 heterodimeric receptor preferentially promotes in vivo expansion of CD8 and NK cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katherine E. Harris ◽  
Kyle J. Lorentsen ◽  
Harbani K. Malik-Chaudhry ◽  
Kaitlyn Loughlin ◽  
Harish Medlari Basappa ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Bispecific Antibody ◽  
T Regulatory Cells ◽  
Tumor Regression ◽  
Interleukin 2 ◽  
In Vivo Studies ◽  
Preferential Binding

AbstractThe use of recombinant interleukin-2 (IL-2) as a therapeutic protein has been limited by significant toxicities despite its demonstrated ability to induce durable tumor-regression in cancer patients. The adverse events and limited efficacy of IL-2 treatment are due to the preferential binding of IL-2 to cells that express the high-affinity, trimeric receptor, IL-2Rαβγ such as endothelial cells and T-regulatory cells, respectively. Here, we describe a novel bispecific heavy-chain only antibody which binds to and activates signaling through the heterodimeric IL-2Rβγ receptor complex that is expressed on resting T-cells and NK cells. By avoiding binding to IL-2Rα, this molecule circumvents the preferential T-reg activation of native IL-2, while maintaining the robust stimulatory effects on T-cells and NK-cells in vitro. In vivo studies in both mice and cynomolgus monkeys confirm the molecule’s in vivo biological activity, extended pharmacodynamics due to the Fc portion of the molecule, and enhanced safety profile. Together, these results demonstrate that the bispecific antibody is a safe and effective IL-2R agonist that harnesses the benefits of the IL-2 signaling pathway as a potential anti-cancer therapy.

scholarly journals Polymorphism in BACH2 gene is a marker of polyglandular autoimmunity

Endocrine ◽  
2021 ◽  
Author(s):  
Marta Fichna ◽  
Magdalena Żurawek ◽  
Bartosz Słomiński ◽  
Marta Sumińska ◽  
Agata Czarnywojtek ◽  
...  
Keyword(s):  
Immune Cell ◽  
Premature Menopause ◽  
Complex Disorders ◽  
Increased Risk ◽  
Organ Specific ◽  
Autoimmune Conditions ◽  
Cell Balance ◽  
Type 3 ◽  
Polyglandular Autoimmunity

Abstract Purpose Genetically predisposed individuals may develop several autoimmune diseases—autoimmune polyendocrine syndromes (APS). APS types 2–4, are complex disorders, which combine various organ-specific autoimmune conditions. Recent reports support the considerable role of the BACH2 gene in immune cell differentiation and shifting the T-cell balance towards regulatory T-cells. BACH2 polymorphisms are associated with autoimmune disorders, including Addison’s disease (AD), Graves’ disease (GD), and probably type 1 diabetes (T1D). Our study was aimed to investigate the BACH2 variant, rs3757247, in endocrine autoimmunity in the Polish population. Methods The analysis comprised 346 individuals with APS, 387 with T1D only, and 568 controls. Genotyping was performed using TaqMan chemistry. Results APS type 2 was found in 219 individuals, type 3 in 102, and type 4 in 25 subjects. Overall, AD was diagnosed in 244 subjects, Hashimoto’s thyroiditis—in 238, T1D—in 127, GD—in 58, vitiligo and chronic gastritis each in 40 patients, celiac disease—in 28, premature menopause in 18, and alopecia in 4 patients. Minor T allele at rs3757247 was found in 56.4% APS vs. 44.1% control alleles (OR 1.59; 95%CI: 1.30–1.95, p < 0.0001). The distribution of genotypes revealed excess TT homozygotes in the APS cohort (33.2 vs. 20.1% in controls, p < 0.0001). The frequencies of rs3757247 alleles and genotypes in T1D patients did not present significant differences vs. controls (p-values > 0.05). Conclusions These results provide evidence of the association between BACH2 polymorphism and polyglandular autoimmunity. Since carriers of rs3757247 display increased risk for additional autoimmune conditions, this variant could identify individuals prone to develop APS.

scholarly journals Monoclonal Antibodies as Neurological Therapeutics

2021 ◽  
Vol 14 (2) ◽  
pp. 92
Author(s):  
Panagiotis Gklinos ◽  
Miranta Papadopoulou ◽  
Vid Stanulovic ◽  
Dimos D. Mitsikostas ◽  
Dimitrios Papadopoulos
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Therapeutic Agents ◽  
Medical Specialties ◽  
Specific Effects ◽  
Different Types ◽  
Neurological Conditions ◽  
Disease Pathways

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.

Sign in / Sign up

Export Citation Format

Share Document