A first-in-human phase I clinical trial investigating the safety and efficacy of repeat dosing MSCTRAIL cell therapy in addition to chemotherapy and immunotherapy in patients with advanced lung cancer
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND AND AIMS: Despite recent progress, advanced non-small cell lung cancer (NSCLC) has poor survival outcomes, necessitating the development of novel therapies. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces cancer cell death and can be delivered to tumors by mesenchymal stromal cells (MSCs) due to the cells' migratory properties. This first-in-human phase I trial assessed safety and dose of umbilical cord-derived MSCs expressing TRAIL (UC-MSCTRAIL) alongside standard NSCLC therapy. METHODS: Participants performance status 0-1 with treatment-naïve, inoperable stage IIIB/IV NSCLC received UC-MSCTRAIL infusions with each cycle of chemotherapy and immunotherapy, up to 3 cycles. A dose de-escalation design was used. Exploratory in vitro and in vivo studies further characterized UC-MSCTRAIL properties. RESULTS: cells/kg). Early termination occurred due to asymptomatic pulmonary emboli (N = 5), which included two patients that were anticoagulated as a protocol amendment with prophylactic low molecular weight heparin (enoxaparin 40 mg) and rivaroxaban 20 mg, respectively. Exploratory analyses found no clear pro-coagulant or immunogenic mechanisms, though participants receiving UC-MSCTRAIL had elevated inflammatory markers. CONCLUSION: This first-in-human study of UC-MSCTRAIL in advanced lung cancer was terminated early due to high prevelance of pulmonary embolism. THough exact mechanism remains unclear, UC-MSCTRAIL may have contributed to a pro-inflammatory environment in participants already at elevated risk of thrombosis due to malignancy. Future MSC-based therapies should incorporate close monitoring for asymptomatic thrombosis and follow a dose escalation design for safety. Safety concerns underscore the need for further research.
Source: Cytotherapy
Authors: Rebecca N. Graham, Alice Davies, Monica L. Mullin, David Gear, Alexander G. Day, Ben Weil, Sarah Benafif, Chuen Ryan Khaw, Hugh Selway-Clarke, Bilyana Popova, Daisuke Yamada, Sarah K. Howlett, Sevasti Galani, Adam Szmul, Anne Riddell, Arjun Nair, Matthew G. Krebs, Tammy Kalber, Joseph Jacob, Pratima Chowdary, Joanne L. Jones, Beth Sage, Graham Wheeler, Krishna Kolluri, Mark W Lowdell, Martin D. Forster, Sam M. Janes
Institutions: University College London, University of British Columbia, Chelsea and Westminster Hospital NHS Foundation Trust, Royal Free London NHS Foundation Trust, University College London Hospitals NHS Foundation Trust, University of Cambridge, The Royal Free Hospital, Manchester Academic Health Science Centre, University of Manchester, The Christie NHS Foundation Trust, University of Aberdeen, NHS Highland, Imperial College London
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,300
Funders: LUNGevity Foundation, AstraZeneca, Wellcome Trust, UCL Hospitals Charitable Foundation, Anthony Nolan, Cancer Research UK, National Institute for Health and Care Research, King's College London, University College London, Astellas Pharma, Astellas Foundation for Research on Metabolic Disorders, University College London Hospitals NHS Foundation Trust, UK Regenerative Medicine Platform, CRUK Lung Cancer Centre of Excellence, Stand Up To Cancer, Imperial Experimental Cancer Medicine Centre, Medical Research Council, Engineering and Physical Sciences Research Council
OpenAlex ID: W7127893759