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Optimizing Siglec-8-Directed Immunotherapy for Eosinophilic and Mast Cell Disorders.
Cancers (Basel)
October 2024
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Current treatments for eosinophilic and mast cell disorders are often ineffective. One promising target to improve outcomes is sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8). As limitations, there are few Siglec-8 monoclonal antibodies (mAbs) available to date, and Siglec-8-directed treatments have so far primarily focused on unconjugated mAbs, which may be inadequate, especially against mast cells.
View Article and Find Full Text PDFControlled adsorption of multiple bioactive proteins enables targeted mast cell nanotherapy.
Nat Nanotechnol
May 2024
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Protein adsorption onto nanomaterials often results in denaturation and loss of bioactivity. Controlling the adsorption process to maintain the protein structure and function has potential for a range of applications. Here we report that self-assembled poly(propylene sulfone) (PPSU) nanoparticles support the controlled formation of multicomponent enzyme and antibody coatings and maintain their bioactivity.
View Article and Find Full Text PDFRegulation of mast cells by overlapping but distinct protein interactions of Siglec-6 and Siglec-8.
Allergy
March 2024
Allakos Inc., San Carlos, California, USA.
Background: Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 and Siglec-8 are closely related mast cell (MC) receptors with broad inhibitory activity, but whose functional differences are incompletely understood.
Methods: Proteomic profiling using quantitative mass spectrometry was performed on primary mouse MCs to identify proteins associated with Siglec-6 and Siglec-8. For functional characterization, each receptor was evaluated biochemically and in ex vivo and in vivo inhibition models of IgE and non-IgE-mediated MC activation in Siglec-6- or Siglec-8-expressing transgenic mice.
Eosinophil Subtypes in Adults with Asthma and Adults with Chronic Obstructive Pulmonary Disease.
Am J Respir Crit Care Med
July 2023
Pulmonary Department, Research Unit, La Candelaria University Hospital, La Laguna University, Carlos III Health Institute Biomedical Research Center, San Cristóbal de La Laguna, Spain.
There is a differential response to eosinophilic modulation between patients with asthma and those with chronic obstructive pulmonary disease (COPD). There is also evidence of different subtypes of eosinophils in murine models. However, no study has compared eosinophil subtypes in individuals with COPD and in those with asthma.
View Article and Find Full Text PDFNovel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy.
Front Immunol
October 2022
Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, University of North Carolina at Chapel Hill (UNC), Chapel Hill, NC, United States.
Background: 10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms.
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