DISEASE MODELING IN INFLAMMATORY BOWEL DISEASE (IBD) USING PATIENT-DERIVED EXPLANTS (PDE) REVEALS CHEMOKINES AS A RELEVANT TARGET OF JAK INHIBITION

• Published in: Inflammatory bowel diseases 2024-01, Vol.30 (Supplement_1), p.S86-S86
• Main Authors: Hristopoulos, Jason, Bilgili, Zeynep, Zhao, Xuanyin, Flier, Sarah, Wolf, Jackqueline, Kantekure, Kanchan, Ono, Yuho, Fabrizio, Anne, Kokkotos, Fotios, Dreyfuss, Jonathan, Crowell, Kristen, Villafuerte, Javier, Messaris, Evangelos, Kokkotou, Efi
• Format: Article
• Language: English
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1093/ibd/izae020.187

Despite a recent explosion of approved drugs for IBD that primarily target cytokines and T-cell trafficking, therapeutic response rates remain low (30-50 %), underscoring the need for more efficacious treatments with fewer side effects. From a drug development perspective, it takes over 10 years for a new drug to reach the market with >90% attrition rates. The realization that drug testing in animal models does not always translate to humans, particularly for complex diseases of high heterogeneity like IBD, leaving a significant gap in pre-clinical drug evaluation. Technologies such as organoids or “gut on a chip” attempted to fulfill this gap, but among their limitations are lack of tissue complexity and an externally induced, and often biased, “disease state” that fails to capture patient heterogeneity and underlying disease mechanisms. We developed a Therapeutic Response Predictor Assay for IBD (TheRPA _ibd) which is based on establishing short term explant cultures from the patient’s diseased tissue (PDE). PDEs can be treated with various candidate drugs or their combinations and inform whether an individual patient is a responder or non-responder to the particular treatment. TheRPA_ibd has been clinically validated for anti-TNF with a predictive accuracy of 0.87 (p