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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2023 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/201090 |
| Online Access: | https://hdl.handle.net/2445/201090 |
| Access Level: | Open access |
| Keyword: | Inhibidors enzimàtics Melanoma Enzyme inhibitors |
| _version_ | 1878732936647278592 |
|---|---|
| author | Spreafico, Anna |
| 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 |
| author_browse | Allen-Vercoe, E. Araujo, Daniel V. Chen, B. Coburn, B. Cochrane, K. Hansen, A. R. Heirali, A. A. Oliva, Marc Saibil, S. D. Schneeberger, Pierre H. H. Sherriff, K. Siu, Lillian L. Spreafico, Anna Stayner, L.-A. Tan, T. J. Wang, B. X. Wong, M. K. Xu, W. |
| 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 |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_4ccbebc2d0d675770ae0cd5bf32efdeb |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/201090 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | Elsevier BV |
| publisherStr | Elsevier BV |
| reponame_str | Dipòsit Digital de la UB |
| 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, 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. Inhibidors enzimàtics Melanoma Enzyme inhibitors 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. Elsevier BV https://hdl.handle.net/2445/201090 |
| 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 |
| status_str | publishedVersion |
| title | 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_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_sort | First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial) |
| topic | Inhibidors enzimàtics Melanoma Enzyme inhibitors |
| topic_facet | Inhibidors enzimàtics Melanoma Enzyme inhibitors |
| url | https://hdl.handle.net/2445/201090 |