Last update 01 Nov 2024

IL-3 x CD molecules x Fibronectin type III domain containing

Last update 01 Nov 2024

Basic Info

Drugs associated with IL-3 x CD molecules x Fibronectin type III domain containing

US20240024479

Patent Mining

Target

CD molecules x Fibronectin type III domain containing x IL-3

Mechanism-

Active Org.

Government of the United States of America

Originator Org.

Government of the United States of America

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IL-3 x CD molecules x Fibronectin type III domain containing

100 Translational Medicine associated with IL-3 x CD molecules x Fibronectin type III domain containing

0 Patents (Medical) associated with IL-3 x CD molecules x Fibronectin type III domain containing

557

Literatures (Medical) associated with IL-3 x CD molecules x Fibronectin type III domain containing

01 Oct 2024·Journal for ImmunoTherapy of Cancer

NSGS mice humanized with cord blood mononuclear cells show sustained and functional myeloid–lymphoid representation with limited graft-versus-host disease

Article

Author: Pradenas, Edwards ; Lázaro-Díez, María ; Prado, Julia G ; Roca Ho, Heleia ; Carcaboso, Ángel M ; Blanco, Julià ; Falgas, Aida ; Martinez-Moreno, Alba ; González-Navarro, Europa Azucena ; Menendez, Pablo ; Carabelli, Julieta ; Juan, Manel ; Panisello, Carla ; Bueno, Clara ; Carrillo, Jorge ; Aschero, Rosario

Humanized immunodeficient mice serve as critical models for investigating the functional interplay between transplanted human cells and a pre-reconstituted human immune system. These models facilitate the study of molecular and cellular pathogenic mechanisms and enable the evaluation of the efficacy and toxicity of immunotherapies, thereby accelerating their preclinical and clinical development. Current strategies rely on inefficient, long-term/delayed hematopoietic reconstitution by CD34+ hematopoietic progenitors or short-term reconstitution with peripheral blood mononuclear cells (PB-MNCs) associated with high rates of graft-versus-host disease (GvHD) and an inefficient representation of immune cell populations. Here, we hypothesized that immunologically naïve cord blood mononuclear cells (CB-MNCs) could serve as a superior alternative, providing long-lasting and functionally effective immune reconstitution. We conducted a comprehensive comparison between the non-obese diabetic (NOD).Cg-Prkdc∧ˆscid-IL2rg∧ˆtm1Wjl/SzJ (NSG) and NSG-Tg(CMV-IL3,CSF2,KITLG)∧ˆ1Eav/MloySzJ (NSGS) immunodeficient mouse models following humanization with either PB-MNCs or CB-MNCs. We assessed the engraftment dynamics of various human immune cells over time and monitored the development of GvHD in both models. For the most promising model, we extensively evaluated immune cell functionalityin vitroandin vivousing sarcoma and leukemia xenografts. Humanizing NSGS mice with CB-MNCs results in a rapid, robust, and sustained representation of a diverse range of functional human lymphoid and myeloid cell populations while minimizing GvHD incidence. In this model, human immune cell populations significantly impair the growth and engraftment of sarcoma and B-cell acute lymphoblastic leukemia cells, with a significant inverse correlation between immune cell levels and tumor growth. This study establishes a fast, efficient, and reliablein vivoplatform for various applications in cancer immunotherapy, particularly for exploring the complex interactions between cancer cells, immune cells, and the tumor microenvironmentin vivo, prior to clinical development.

02 Apr 2024·Growth Factors

Interleukin-3 production by basal-like breast cancer cells is associated with poor prognosis

Article

Author: Lindeman, Geoffrey J. ; Thompson, Emma J. ; Ingman, Wendy V. ; Gregory, Philip A. ; Escarbe, Samantha ; Khew-Goodall, Yeesim ; Bonder, Claudine S. ; Farshid, Gelareh ; Madden, Stephen ; Lim, Elgene ; Tvorogov, Denis ; Lopez, Angel F.

Breast cancer represents a collection of pathologies with different molecular subtypes, histopathology, risk factors, clinical behavior, and responses to treatment. "Basal-like" breast cancers predominantly lack the receptors for estrogen and progesterone (ER/PR), lack amplification of human epidermal growth factor receptor 2 (HER2) but account for 10-15% of all breast cancers, are largely insensitive to targeted treatment and represent a disproportionate number of metastatic cases and deaths. Analysis of interleukin (IL)-3 and the IL-3 receptor subunits (IL-3RA + CSF2RB) reveals elevated expression in predominantly the basal-like group. Further analysis suggests that IL-3 itself, but not the IL-3 receptor subunits, associates with poor patient outcome. Histology on patient-derived xenografts supports the notion that breast cancer cells are a significant source of IL-3 that may promote disease progression. Taken together, these observations suggest that IL-3 may be a useful marker in solid tumors, particularly triple negative breast cancer, and warrants further investigation into its contribution to disease pathogenesis.

01 Mar 2024·Journal of Allergy and Clinical Immunology

Dual inhibition of airway inflammation and fibrosis by common β cytokine receptor blockade

Article

Author: Bozinovski, Steven ; Wilson, Nick ; Cildir, Gökhan ; Keam, Simon P ; Vlahos, Ross ; Toubia, John ; Yip, Kwok Ho ; Hercus, Timothy R ; Pant, Harshita ; Wang, Hao ; Kral, Anita C ; Wark, Peter ; Owczarek, Catherine ; Tumes, Damon J ; Nichol, Kristy ; Lopez, Angel F

BACKGROUNDPatients with severe asthma can present with eosinophilic type 2 (T2), neutrophilic, or mixed inflammation that drives airway remodeling and exacerbations and represents a major treatment challenge. The common β (βc) receptor signals for 3 cytokines, GM-CSF, IL-5, and IL-3, which collectively mediate T2 and neutrophilic inflammation.OBJECTIVETo determine the pathogenesis of βc receptor-mediated inflammation and remodeling in severe asthma and to investigate βc antagonism as a therapeutic strategy for mixed granulocytic airway disease.METHODSβc gene expression was analyzed in bronchial biopsy specimens from patients with mild-to-moderate and severe asthma. House dust mite extract and Aspergillus fumigatus extract (ASP) models were used to establish asthma-like pathology and airway remodeling in human βc transgenic mice. Lung tissue gene expression was analyzed by RNA sequencing. The mAb CSL311 targeting the shared cytokine binding site of βc was used to block βc signaling.RESULTSβc gene expression was increased in patients with severe asthma. CSL311 potently reduced lung neutrophils, eosinophils, and interstitial macrophages and improved airway pathology and lung function in the acute steroid-resistant house dust mite extract model. Chronic intranasal ASP exposure induced airway inflammation and fibrosis and impaired lung function that was inhibited by CSL311. CSL311 normalized the ASP-induced fibrosis-associated extracellular matrix gene expression network and strongly reduced signatures of cellular inflammation in the lung.CONCLUSIONSβc cytokines drive steroid-resistant mixed myeloid cell airway inflammation and fibrosis. The anti-βc antibody CSL311 effectively inhibits mixed T2/neutrophilic inflammation and severe asthma-like pathology and reverses fibrosis gene signatures induced by exposure to commonly encountered environmental allergens.

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IL-3 x CD molecules x Fibronectin type III domain containing

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