Autologous P63+ lung progenitor cell transplantation in idiopathic pulmonary fibrosis: a phase 1 clinical trial

Abstract

In idiopathic pulmonary fibrosis (IPF) patients, alveolar epithelium architectures are persistently lost and lung gas transfer function would decline over time, which cannot be rescued by conventional anti-fibrotic therapy. P63+ airway basal progenitor cells are previously reported to have great potential to repair damaged lung epithelium. Here, we successfully cloned and expanded the autologous P63+ progenitor cells from IPF patients to manufacture the cell therapeutic product REGEND001, which were further characterized by cell morphology and single-cell transcriptomic analysis. Subsequently, an open-label, dose-escalation exploratory clinical trial was conducted (CTR20210349). The primary outcome was the incidence and severity of the cell therapy-related adverse events (AEs); secondary outcome included other safety and efficacy evaluation in each dose groups. We treated 12 patients with ascending doses of cells: 0.6x, 1x, 2x and 3.3x 10 6 cells/kg bodyweight. The data revealed that P63+ basal progenitor cell was safe and well tolerated at all doses, with no dose-limiting toxicity or cell therapy-related severe adverse events observed. Patients in the three higher dose groups showed statistically significant improvement of lung gas transfer function as well as exercise ability after REGEND001 therapy. Resolution of honeycomb lesion was also observed in patients of higher dose groups. Altogether these initial results indicated that REGEND001 has a high safety profile and meanwhile shows preliminary efficacy in IPF patients.