Pre-clinical proof-of-concept of anti-fibrotic activity of caveolin-1 scaffolding domain peptide LTI-03 in ex vivo precision cut lung slices from patients with Idiopathic Pulmonary Fibrosis

Human lung tissues from idiopathic pulmonary fibrosis (IPF) patients undergoing lung transplantation and non-IPF donors were obtained via the European IPF Registry (euIPFreg) sites Vienna and Giessen and delivered via the European IPF Biobank or the UGMLC Biobank, a member of the DZL platform biobanking. The study protocol was approved by the Ethics Committee of the Justus-Liebig University School of Medicine (No. 111/08: European IPF Registry and 58/15: UGMLC Giessen Biobank), and informed consent was obtained in written form from each subject (a comprehensive list of patient data and applied assays is provided in Table 2). Lung biopsy cores were obtained exclusively from 8 patients undergoing lung transplant for treatment of IPF and processed for PCLS culture as previously described18. All patients were male, an average of 61.5 years of age (std dev 6.56 years), and had a clinical diagnosis of IPF alone, or IPF with secondary pulmonary hypertension (PH). Usual interstitial pneumonia (UIP) was the main pathological finding on all explant tissue. LTI-03 was added in PCLS culture media at 0.3, 5.0, or 10 μM for treatments. The inactive control peptide CP at 10 μM while Nintedanib was prepared in a 1 mM stock solution with sterile filtered DMSO and used at 1 μM. PCLS were treated every 12hrs and supernatant and tissue was harvested 12 hours following the last of either three (day 2) or nine treatments (day 5).