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

23 Citations (Scopus)

22 Downloads (Pure)

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

Access to Document

10.1038/s41591-019-0599-8Licence: Unspecified

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

Link to publication in Scopus

Fingerprint Dive into the research topics of 'Safety profile of autologous macrophage therapy for liver cirrhosis'. Together they form a unique fingerprint.

Francesca Moroni
- Institute of Medical Sciences
Person

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.

@article{297a270f21204637a85d713fe132d2ff,

title = "Safety profile of autologous macrophage therapy for liver cirrhosis",

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.",

keywords = "regeneration, translational research, DIAGNOSIS, MARKER, DISEASE, INJURY, FUNCTIONAL-CHARACTERIZATION, CELL THERAPY, DUCTULAR REACTIONS, TRANSPLANTATION",

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

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. ",

year = "2019",

month = oct,

doi = "10.1038/s41591-019-0599-8",

language = "English",

volume = "25",

pages = "1560--1565",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

}

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

C2 - 31591593

VL - 25

SP - 1560

EP - 1565

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

ER -