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 Nielsen; Kishwar Musa; Jonathan A Fallowfield; Stuart J Forbes

doi:10.1038/s41591-019-0599-8

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 journal › Article › peer-review

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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 language	English
Pages (from-to)	1560-1565
Number of pages	6
Journal	Nature Medicine
Volume	25
Early online date	7 Oct 2019
DOIs	https://doi.org/10.1038/s41591-019-0599-8
Publication status	Published - Oct 2019

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Moroni_et_al_NM_safety_profile_autologous_AAM
This is the author's accepted manuscript of an article published in Nature Medicine on 07 Oct 2019. The final published version is available at: https://doi.org/10.1038/s41591-019-0599-8.
Accepted author manuscript, 820 KBLicence: Unspecified
Forbes_Fig1Accepted author manuscript, 172 KBLicence: Unspecified
Forbes_Fig2Accepted author manuscript, 110 KBLicence: Unspecified
Forbes_Fig3Accepted author manuscript, 181 KBLicence: Unspecified

Cite this

Moroni, F., Dwyer, B. J., Graham, C., Pass, C., Bailey, L., Ritchie, L., Mitchell, D., Glover, A., Laurie, A., Doig, S., Hargreaves, E., Fraser, A. R., Turner, M. L., Campbell, J. D. M., McGowan, N. W. A., Barry, J., Moore, J. K., Hayes, P. C., Leeming, D. J., ... Forbes, S. J. (2019). Safety profile of autologous macrophage therapy for liver cirrhosis. Nature Medicine, 25, 1560-1565. https://doi.org/10.1038/s41591-019-0599-8

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 › peer-review

Moroni, F, Dwyer, BJ, Graham, C, Pass, C, Bailey, L, Ritchie, L, Mitchell, D, Glover, A, Laurie, A, Doig, S, Hargreaves, E, Fraser, AR, Turner, ML, Campbell, JDM, McGowan, NWA, Barry, J, Moore, JK, Hayes, PC, Leeming, DJ, Nielsen, MJ, Musa, K, Fallowfield, JA & Forbes, SJ 2019, 'Safety profile of autologous macrophage therapy for liver cirrhosis', Nature Medicine, vol. 25, pp. 1560-1565. https://doi.org/10.1038/s41591-019-0599-8

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. / Safety profile of autologous macrophage therapy for liver cirrhosis. In: Nature Medicine. 2019 ; Vol. 25. pp. 1560-1565.

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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.",

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Safety profile of autologous macrophage therapy for liver cirrhosis

Abstract

Keywords

UN SDGs

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