Safety profile of autologous macrophage therapy for liver cirrhosis

Francesca Moroni, Benjamin J Dwyer, Catriona Graham, Chloe Pass, Laura Bailey, Lisa Ritchie, Donna Mitchell, Alison Glover, Audrey Laurie, Stuart Doig, Emily Hargreaves, Alasdair R Fraser, Marc L Turner, John D M Campbell, Neil W A McGowan, Jacqueline Barry, Joanna K Moore, Peter C Hayes, Diana J Leeming, Mette J NielsenKishwar Musa, Jonathan A Fallowfield, Stuart J Forbes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)
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Abstract

Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 107, 108 or up to 109 cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.

Original languageEnglish
Pages (from-to)1560-1565
Number of pages6
JournalNature Medicine
Volume25
Early online date7 Oct 2019
DOIs
Publication statusPublished - Oct 2019

Bibliographical note

This work was supported by a Medical Research Council UK grant (Biomedical Catalyst Major Awards Committee; reference MR/M007588/1) to S.J. Forbes. We thank Z.M. Younossi (Center for Outcomes Research in Liver Diseases, Washington, DC, USA) for academic use of the CLDQ instrument and L.J. Fallowfield (Sussex Health Outcomes Research & Education in Cancer (SHORE-C), University of Sussex, UK) for advice about health-related quality of life assessment.

Keywords

  • regeneration
  • translational research
  • DIAGNOSIS
  • MARKER
  • DISEASE
  • INJURY
  • FUNCTIONAL-CHARACTERIZATION
  • CELL THERAPY
  • DUCTULAR REACTIONS
  • TRANSPLANTATION

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