First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)

Background: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI resp...

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Autores: Spreafico, Anna, Heirali, A. A., Araujo, Daniel V., Tan, T. J., Oliva, Marc, Schneeberger, Pierre H. H., Chen, B., Wong, M. K., Stayner, L.-A., Hansen, A. R., Saibil, S. D., Wang, B. X., Cochrane, K., Sherriff, K., Allen-Vercoe, E., Xu, W., Siu, Lillian L., Coburn, B.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/201090
Acceso en línea:https://hdl.handle.net/2445/201090
Access Level:acceso abierto
Palabra clave:Inhibidors enzimàtics
Melanoma
Enzyme inhibitors
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spelling First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)Spreafico, AnnaHeirali, A. A.Araujo, Daniel V.Tan, T. J.Oliva, MarcSchneeberger, Pierre H. H.Chen, B.Wong, M. K.Stayner, L.-A.Hansen, A. R.Saibil, S. D.Wang, B. X.Cochrane, K.Sherriff, K.Allen-Vercoe, E.Xu, W.Siu, Lillian L.Coburn, B.Inhibidors enzimàticsMelanomaEnzyme inhibitorsMelanomaBackground: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use.Patients and methods: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.Results: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids.Conclusions: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.Elsevier BV2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/201090Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.annonc.2023.02.011Annals of Oncology, 2023, vol. 34, num. 6, p. 520-530https://doi.org/10.1016/j.annonc.2023.02.011cc by-nc-nd (c) Spreafico, Anna et al, 2023http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2010902026-05-27T06:46:51Z
dc.title.none.fl_str_mv First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)
title First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)
spellingShingle First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)
Spreafico, Anna
Inhibidors enzimàtics
Melanoma
Enzyme inhibitors
Melanoma
title_short First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)
title_full First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)
title_fullStr First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)
title_full_unstemmed First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)
title_sort First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)
dc.creator.none.fl_str_mv Spreafico, Anna
Heirali, A. A.
Araujo, Daniel V.
Tan, T. J.
Oliva, Marc
Schneeberger, Pierre H. H.
Chen, B.
Wong, M. K.
Stayner, L.-A.
Hansen, A. R.
Saibil, S. D.
Wang, B. X.
Cochrane, K.
Sherriff, K.
Allen-Vercoe, E.
Xu, W.
Siu, Lillian L.
Coburn, B.
author Spreafico, Anna
author_facet Spreafico, Anna
Heirali, A. A.
Araujo, Daniel V.
Tan, T. J.
Oliva, Marc
Schneeberger, Pierre H. H.
Chen, B.
Wong, M. K.
Stayner, L.-A.
Hansen, A. R.
Saibil, S. D.
Wang, B. X.
Cochrane, K.
Sherriff, K.
Allen-Vercoe, E.
Xu, W.
Siu, Lillian L.
Coburn, B.
author_role author
author2 Heirali, A. A.
Araujo, Daniel V.
Tan, T. J.
Oliva, Marc
Schneeberger, Pierre H. H.
Chen, B.
Wong, M. K.
Stayner, L.-A.
Hansen, A. R.
Saibil, S. D.
Wang, B. X.
Cochrane, K.
Sherriff, K.
Allen-Vercoe, E.
Xu, W.
Siu, Lillian L.
Coburn, B.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Inhibidors enzimàtics
Melanoma
Enzyme inhibitors
Melanoma
topic Inhibidors enzimàtics
Melanoma
Enzyme inhibitors
Melanoma
description Background: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use.Patients and methods: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.Results: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids.Conclusions: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/201090
url https://hdl.handle.net/2445/201090
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.annonc.2023.02.011
Annals of Oncology, 2023, vol. 34, num. 6, p. 520-530
https://doi.org/10.1016/j.annonc.2023.02.011
dc.rights.none.fl_str_mv cc by-nc-nd (c) Spreafico, Anna et al, 2023
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Spreafico, Anna et al, 2023
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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