scholarly journals Natural killer cells in inflammatory autoimmune diseases

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Yuyan Yang ◽  
Jessica Day ◽  
Fernando Souza‐Fonseca Guimaraes ◽  
Ian P Wicks ◽  
Cynthia Louis
Keyword(s):  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Killer Cells ◽  
Inflammatory Autoimmune Diseases

Natural Killer Cells in Autoimmune Diseases

1992 ◽  
pp. 59-69
Author(s):  
Dag Sørskaar ◽  
Øystein Førre
Keyword(s):  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Killer Cells

scholarly journals Natural killer cells in human autoimmune diseases

Immunology ◽  
2010 ◽  
Vol 131 (4) ◽  
pp. 451-458 ◽  
Author(s):  
Nicolas Schleinitz ◽  
Frédéric Vély ◽  
Jean-Robert Harlé ◽  
Eric Vivier
Keyword(s):  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Killer Cells

Flip‐flops of natural killer cells in autoimmune diseases versus cancers: Immunologic axis

2019 ◽  
Vol 234 (10) ◽  
pp. 16998-17010 ◽  
Author(s):  
Saeid Shahrabi ◽  
Zeinab D. Zayeri ◽  
Narges Ansari ◽  
Elham H. Hadad ◽  
Elham Rajaei
Keyword(s):  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Killer Cells

scholarly journals Editorial: The Role of Natural Killer Cells in Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Alessandra Fierabracci ◽  
Domenico V. Delfino ◽  
Mary A. Markiewicz ◽  
Antonio La Cava
Keyword(s):  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Killer Cells

Natural killer cells in atopic and autoimmune diseases of the skin

2010 ◽  
Vol 125 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Dagmar von Bubnoff ◽  
Emmanuel Andrès ◽  
François Hentges ◽  
Thomas Bieber ◽  
Tatiana Michel ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Killer Cells

scholarly journals The role of natural killer cells in pathogenesis of autoimmune diseases

2015 ◽  
Vol 4 ◽  
pp. 470-476 ◽  
Author(s):  
Katarzyna Popko ◽  
Elżbieta Górska
Keyword(s):  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Killer Cells

scholarly journals OP0023 GENERATION OF PT101, A HIGHLY SELECTIVE IL-2 MUTEIN FOR TREATMENT OF AUTOIMMUNE DISEASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 13.1-13
Author(s):  
J. Visweswaraiah ◽  
E. Sampson ◽  
P. Petaipimol ◽  
A. Monsef ◽  
K. Kis-Toth ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Cytokine Production ◽  
Immune Cell ◽  
Cell Types ◽  
Killer Cells

Background:Regulatory T cells (Tregs) play a critical role in immune homeostasis and are dysfunctional in many autoimmune diseases. Interleukin 2 (IL-2) drives the proliferation and function of Tregs. via the heterotrimeric IL-2 receptor (CD25/CD122/CD132). As a result, CD25 loss-of-function in mice is associated with Treg deficiency and widespread autoimmunity. Low dose IL-2 is being evaluated for treatment of autoimmune diseases and has been shown to expand Tregs, however it has a narrow selectivity window before activating conventional T cells and natural killer cells. To enhance IL-2 selectivity and improve its therapeutic utility for activating and expanding Tregs, mutations can be introduced that reduce CD122/CD132 affinity thus creating a dependency on CD25 binding for signaling through CD122/CD132 upon IL-2 facilitated CD25/CD122/CD132 trimer formation.Objectives:To generate a highly selective IL-2 mutein that activates and expands Tregs selectively that can be used for treatment of autoimmune diseasesMethods:Using a structure guided approach, we introduced mutations in IL-2 that significantly decreased CD122 binding affinity in addition to other mutations that increased CD25 binding affinity. Finally, we explored additional mutations, format, orientation, and linker lengths to generate the most potent, selective molecule with drug-like manufacturability. These structure activity relationship efforts culminated in the generation of PT101, a mutant IL-2 Fc fusion that is selective in activating and expanding Tregs in vitro and in vivo.Results:PT101 selectively induced STAT5 phosphorylation in human and cynomolgus monkey Tregs in vitro. In humanized NOD-scid IL-2Rg-null (NSG) mice and cynomolgus monkeys, administration of PT101 dose-dependently and selectively expanded Tregs without significant effects on other immune cell types, and without eliciting proinflammatory cytokine production. The Tregs from PT101-dosed humanized mice have increased expression of FOXP3 and CD25, suggesting enhanced function and stability. In a Phase 1a single ascending dose clinical trial, PT101 was well-tolerated and selectively expanded total Tregs, with a mean maximal increase of up to 3.6-fold over baseline in healthy volunteers. There was no evidence of expansion of natural killer cells nor pro-inflammatory conventional T cells at any of the doses studied.Conclusion:PT101 selectively activated and expanded Tregs without significant effects on other immune cell types, and without eliciting proinflammatory cytokine production. These Tregs have enhanced function and stability as seen by increase in expression of FOXP3 and CD25 in these cells. PT101 maintained selectivity in Phase 1 a clinical trial with no evidence of expansion of natural killer cells nor pro-inflammatory conventional T at any dose studied. A Phase 1b/2a clinical trial in patients with ulcerative colitis and a Phase 2 clinical trial in patients with systemic lupus erythematosus are planned to further evaluate PT101.Disclosure of Interests:None declared

1569: BCG Resistant Bladder Urothelial Carcinoma Under-Expresses Ligands for Natural Cytotoxicity Receptors of Natural Killer Cells

2007 ◽  
Vol 177 (4S) ◽  
pp. 518-518
Author(s):  
Vladimir Yutkin ◽  
Dov Pode ◽  
Tal I. Arnon ◽  
Eli Pikarsky ◽  
Ofer Mandelboim
Keyword(s):  
Natural Killer Cells ◽  
Urothelial Carcinoma ◽  
Natural Killer ◽  
Natural Cytotoxicity ◽  
Killer Cells ◽  
Bladder Urothelial Carcinoma ◽  
Natural Cytotoxicity Receptors
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