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 language | English |
|---|---|
| Pages (from-to) | 1560-1565 |
| Number of pages | 6 |
| Journal | Nature Medicine |
| Volume | 25 |
| Early online date | 7 Oct 2019 |
| DOIs | |
| Publication status | Published - Oct 2019 |
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Keywords
- regeneration
- translational research
- DIAGNOSIS
- MARKER
- DISEASE
- INJURY
- FUNCTIONAL-CHARACTERIZATION
- CELL THERAPY
- DUCTULAR REACTIONS
- TRANSPLANTATION
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Safety profile of autologous macrophage therapy for liver cirrhosis. / Moroni, Francesca; Dwyer, Benjamin J; Graham, Catriona; Pass, Chloe; Bailey, Laura; Ritchie, Lisa; Mitchell, Donna; Glover, Alison; Laurie, Audrey; Doig, Stuart; Hargreaves, Emily; Fraser, Alasdair R; Turner, Marc L; Campbell, John D M; McGowan, Neil W A; Barry, Jacqueline; Moore, Joanna K; Hayes, Peter C; Leeming, Diana J; Nielsen, Mette J; Musa, Kishwar; Fallowfield, Jonathan A; Forbes, Stuart J.
In: Nature Medicine, Vol. 25, 10.2019, p. 1560-1565.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Safety profile of autologous macrophage therapy for liver cirrhosis
AU - Moroni, Francesca
AU - Dwyer, Benjamin J
AU - Graham, Catriona
AU - Pass, Chloe
AU - Bailey, Laura
AU - Ritchie, Lisa
AU - Mitchell, Donna
AU - Glover, Alison
AU - Laurie, Audrey
AU - Doig, Stuart
AU - Hargreaves, Emily
AU - Fraser, Alasdair R
AU - Turner, Marc L
AU - Campbell, John D M
AU - McGowan, Neil W A
AU - Barry, Jacqueline
AU - Moore, Joanna K
AU - Hayes, Peter C
AU - Leeming, Diana J
AU - Nielsen, Mette J
AU - Musa, Kishwar
AU - Fallowfield, Jonathan A
AU - Forbes, Stuart J
N1 - 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.
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - regeneration
KW - translational research
KW - DIAGNOSIS
KW - MARKER
KW - DISEASE
KW - INJURY
KW - FUNCTIONAL-CHARACTERIZATION
KW - CELL THERAPY
KW - DUCTULAR REACTIONS
KW - TRANSPLANTATION
UR - http://www.scopus.com/inward/record.url?scp=85074194479&partnerID=8YFLogxK
U2 - 10.1038/s41591-019-0599-8
DO - 10.1038/s41591-019-0599-8
M3 - Article
VL - 25
SP - 1560
EP - 1565
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
ER -