Last update 01 Nov 2024

CD3 x IL-5Rα

Last update 01 Nov 2024

Basic Info

Related Targets

CD3IL-5Rα

Drugs associated with CD3 x IL-5Rα

ND-003

Target

CD3 x IL-5Rα

Mechanism

CD3 stimulants [+1]

Active Org.-

Originator Org.

Numab Innovation AG

Active Indication-

Inactive Indication

Asthma

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CD3 x IL-5Rα

100 Translational Medicine associated with CD3 x IL-5Rα

0 Patents (Medical) associated with CD3 x IL-5Rα

Literatures (Medical) associated with CD3 x IL-5Rα

01 Jan 2024·International Immunopharmacology

Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease

Article

Author: Nelson, Amy J ; May, Sara M ; Gleason, Angela ; Romberger, Debra J ; De Graaff, Joel Van ; Schwab, Aaron ; Thiele, Geoffrey M ; Walenz, Rhonda ; Bailey, Kristina L ; Poole, Jill A ; Mikuls, Ted R ; Hershberger, Daniel ; Kramer, Bridget ; Cole, Kathryn E ; Talmadge, James E ; Gaurav, Rohit ; Duryee, Michael J ; England, Bryant R

OBJECTIVESInterstitial lung disease (ILD) is associated with significant mortality in rheumatoid arthritis (RA) patients with key cellular players remaining largely unknown. This study aimed to characterize inflammatory and myeloid derived suppressor cell (MDSC) subpopulations in RA-ILD as compared to RA, idiopathic pulmonary fibrosis (IPF) without autoimmunity, and controls.METHODSPeripheral blood was collected from patients with RA, RA-ILD, IPF, and controls (N = 60, 15/cohort). Myeloid cell subpopulations were identified phenotypically by flow cytometry using the following markers:CD45,CD3,CD19,CD56,CD11b,HLA-DR,CD14,CD16,CD15,CD125,CD33. Functionality of subsets were identified with intracellular arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression.RESULTSThere was increased intermediate (CD14⁺⁺CD16⁺) and nonclassical (CD14^+/-CD16⁺⁺) and decreased classical (CD14⁺⁺CD16^-) monocytes in RA, RA-ILD, and IPF vs. control. Intermediate monocytes were higher and classical monocytes were lower in RA-ILD vs. RA but not IPF. Monocytic (m)MDSCs were higher in RA-ILD vs. control and RA but not IPF. Granulocytic (g)MDSCs did not significantly differ. In contrast, neutrophils were increased in IPF and RA-ILD patients with elevated expression of Arg-1 sharing similar dimensional clustering pattern. Eosinophils were increased in RA-ILD vs. controls, RA and IPF. Across cohorts, iNOS was decreased in intermediate/nonclassical monocytes but increased in mMDSCs vs. classical monocytes. In RA-ILD, iNOS positive mMDSCs were increased versus classic monocytes.CONCLUSIONSMyeloid cell subpopulations are significantly modulated in RA-ILD patients with expansion of CD16⁺ monocytes, mMDSCs, and neutrophils, a phenotypic profile more aligned with IPF than other RA patients. Eosinophil expansion was unique to RA-ILD, potentially facilitating disease pathogenesis and providing a future therapeutic target.

01 Oct 2023·Clinical Immunology

Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of severe eosinophilic asthma

Article

Author: Kim, Dae-Seong ; Kim, Yong-Sung ; Park, Hae-Sim ; Kim, Jun-Ho

Severe eosinophilic asthma (SEA) is characterized by elevated eosinophil counts in the blood and airway mucosa. While monoclonal antibody therapies targeting interleukin-5 (IL-5) and its receptor (IL-5Rα) have improved treatment, some patients remain unresponsive. We propose an alternative approach to eliminate eosinophils using T cells by engineering IL-5Rα × CD3 bispecific T-cell engagers (bsTCEs) that target both IL-5Rα on eosinophils and CD3 on T cells. We designed different formats of IL-5Rα × CD3 bsTCEs, incorporating variations in valency, geometry, and affinity for the target antigen binding. We identified the single-chain variable fragment (scFv)-Fc format with the highest affinity toward the membrane-proximal domain of IL-5Rα in the IL-5Rα-binding arm showed the most potent cytotoxicity against IL-5Rα-expressing peripheral eosinophils by activating autologous primary T cells from healthy donors. This study proposes IL-5Rα × CD3 bsTCEs as potential alternatives for SEA treatment. Importantly, it demonstrates the first application of bsTCEs in eliminating disease-associated cells, including eosinophils, beyond cancer cells.

01 May 2021·Allergy

Basophil activation and serum IL‐5 levels as possible monitor biomarkers in severe eosinophilic asthma patients treated with anti‐IL‐5 drugs

Letter

Author: Gasbarrini, Antonio ; Tolusso, Barbara ; Di Mario, Clara ; Pentassuglia, Antonella ; Romano, Antonino ; Rumi, Gabriele ; Gremese, Elisa ; Caruso, Cristiano ; Colantuono, Stefania

This study investigated the correlation between clin. response to mepolizumab or benralizumab and potential predictive biomarkers such as the serum IL-5 levels and the phenotype of circulating basophils in eosinophilic asthma (EA) patients.They enrolled 19 patients older than 18 years, who came to the Allergy Unit of the Columbus Hospital in Rome between Jan. 2018 and June 2019 because of severe EA and for each patient clin. and laboratory evaluations were performed at baseline (T0) and after 3 (T3) and 6 mo of treatment (T6).Patients were treated with mepolizumab or benralizumab according to data sheet (GINA and ERS/ATS guidelines).A complete response was observed in 13 patients (68.4%) and a partial response in 6 (31.6%), regardless of the treatment used (ie, mepolizumab or benralizumab).During the 6 mo of follow-up, neither exacerbations nor hospitalization was observed and OCS was progressively reduced and finally stopped in 14 (73.7%) out of 19 patients at T6; moreover, a substantial reduction was achieved in the others.Interestingly, here, the lower was the rate of the endotype CD3neg CRTH2pos CD203cpos CD12 pos of activated basophil at baseline, the better was the clin. response at T6 in patients treated with an anti-IL5 biol. therapy.In this pilot study the cohort of EA patients shows that the rate of activated basophils, in particular of those that express CD125, is inversely related to the effectiveness of anti-IL5/IL5Rα drugs, proving to be a biomarker that allows identification of the patient's phenotype that better respond to therapy and, at the same time, the patient's phenotype that requires the concomitant use of OCS.

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