Profiling Immune Responses to Improve Therapeutics

Profiling immune responses in severe asthma patients before and after biologic treatment to identify biomarkers of response and novel drug targets.
Ongoing Allergic & Atopic Diseases Biomarker Discovery Disease Subtyping Experimental Platforms & Models Human Cohorts Immune Profiling Precision Medicine Translational & Clinical

Funding Year: 2024

Project Overview

Asthma is a chronic autoinflammatory disease affecting up to 10% of adults, with severe cases often unresponsive to conventional therapies. While biologics have improved control for some patients, no efficacious treatments exist for those who do not respond. This project leverages the resources and expertise of Immune Health to analyze blood samples from 60 patients with severe asthma before and after approximately four weeks of biologic treatment — identifying immune profile clusters at baseline and tracking changes associated with treatment response. The work aims to identify candidate biomarkers for biologic drug response and uncover novel drug targets for patients ineligible for currently available biologics. Patient enrollment is ongoing. Note: This project was originally awarded to Blanca Himes, PhD; the award was transferred to Patrick Gleeson, MD in December 2024 following Dr. Himes' appointment as Senior Advisor, Data Science at the NHLBI.

Impact & Innovation

Decoding why biologics work for some asthma patients — and not others

 

By profiling immune responses in severe asthma patients before and after biologic treatment, this project builds the evidence base needed to match patients to therapies and identify new targets for those current biologics cannot reach.

  • Addresses the significant unmet need in severe asthma where a substantial proportion of patients do not respond to available biologic therapies
  • Generates candidate biomarkers for biologic drug response and novel drug targets through immune profiling of a well-characterized severe asthma patient cohort
  • Advances the Consortium’s Integrated Data and Discovery Platforms pillar by building a clinically annotated immune profiling dataset that can inform precision treatment strategies across autoinflammatory airway disease
Research Approach

A framework designed for discovery

This project applies immune profiling to blood samples from severe asthma patients at baseline and following biologic treatment to identify immune clusters associated with treatment response and uncover novel therapeutic targets for non-responders. The work leverages the clinical and analytical infrastructure of Immune Health at Penn.

Blood sample collection from 60 severe asthma patients before and approximately four weeks after biologic treatment initiation; immune profiling to identify baseline clusters and treatment-associated immune changes; and computational analysis to identify candidate biomarkers of biologic drug response and novel drug targets for biologic-ineligible patients.

Blood samples from 60 severe asthma patients meeting specific clinical and laboratory criteria for biologic eligibility, paired pre- and post-treatment immune profiling datasets, and Immune Health resources and expertise for sample analysis and data integration.

Identification of immune profile clusters that predict biologic treatment response in severe asthma, and discovery of novel drug targets for patients who do not respond to currently available biologics. Findings are intended to support precision matching of patients to therapies and inform the next generation of asthma biologic development. Note: patient enrollment is ongoing and outcomes have not yet been evaluated.

Investigators & Institutions

Powering the science

Principal Investigator

Patrick Kevin Gleeson, MD, MSCE, Colton Consortium Member

NRSA Postdoctoral Fellow, Department of Medicine (Pulmonary, Allergy and Critical Care), Perelman School of Medicine, University of Pennsylvania

Colton Centers & Institutions

Colton Center for Autoimmunity at the University of Pennsylvania

Perelman School of Medicine