Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1
Abstract Despite the capability of extracellular vesicles (EVs) derived from Gram‐negative and Gram‐positive bacteria to induce potent anti‐tumour responses, large‐scale production of bacterial EVs remains as a hurdle for their development as novel cancer immunotherapeutic agents. Here, we developed...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-08-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12357 |
| _version_ | 1797667813128667136 |
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| author | Solchan Won Changjin Lee Seoyoon Bae Jaemin Lee Dongsic Choi Min‐Gang Kim Sunghyun Song Jaewook Lee Eunhye Kim HaYoung Shin Anita Basukala Tae Ryong Lee Dong‐Sup Lee Yong Song Gho |
| author_facet | Solchan Won Changjin Lee Seoyoon Bae Jaemin Lee Dongsic Choi Min‐Gang Kim Sunghyun Song Jaewook Lee Eunhye Kim HaYoung Shin Anita Basukala Tae Ryong Lee Dong‐Sup Lee Yong Song Gho |
| author_sort | Solchan Won |
| collection | DOAJ |
| description | Abstract Despite the capability of extracellular vesicles (EVs) derived from Gram‐negative and Gram‐positive bacteria to induce potent anti‐tumour responses, large‐scale production of bacterial EVs remains as a hurdle for their development as novel cancer immunotherapeutic agents. Here, we developed manufacturing processes for mass production of Escherichia coli EVs, namely, outer membrane vesicles (OMVs). By combining metal precipitation and size‐exclusion chromatography, we isolated 357 mg in total protein amount of E. coli OMVs, which was equivalent to 3.93 × 1015 particles (1.10 × 1010 particles/μg in total protein amounts of OMVs) from 160 L of the conditioned medium. We show that these mass‐produced E. coli OMVs led to complete remission of two mouse syngeneic tumour models. Further analysis of tumour microenvironment in neoantigen‐expressing tumour models revealed that E. coli OMV treatment causes increased infiltration and activation of CD8+ T cells, especially those of cancer antigen‐specific CD8+ T cells with high expression of TCF‐1 and PD‐1. Furthermore, E. coli OMVs showed synergistic anti‐tumour activity with anti‐PD‐1 antibody immunotherapy, inducing substantial tumour growth inhibition and infiltration of activated cancer antigen‐specific stem‐like CD8+ T cells into the tumour microenvironment. These data highlight the potent anti‐tumour activities of mass‐produced E. coli OMVs as a novel candidate for developing next‐generation cancer immunotherapeutic agents. |
| first_indexed | 2024-03-11T20:19:58Z |
| format | Article |
| id | doaj.art-f9dfe70f748040b693b4c049562d6fd2 |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-03-11T20:19:58Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-f9dfe70f748040b693b4c049562d6fd22023-10-03T09:15:53ZengWileyJournal of Extracellular Vesicles2001-30782023-08-01128n/an/a10.1002/jev2.12357Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1Solchan Won0Changjin Lee1Seoyoon Bae2Jaemin Lee3Dongsic Choi4Min‐Gang Kim5Sunghyun Song6Jaewook Lee7Eunhye Kim8HaYoung Shin9Anita Basukala10Tae Ryong Lee11Dong‐Sup Lee12Yong Song Gho13Department of Biomedical Sciences Seoul National University College of Medicine SeoulRepublic of KoreaSL Bigen Inc. IncheonRepublic of KoreaDepartment of Life Sciences POSTECH PohangRepublic of KoreaSL Bigen Inc. IncheonRepublic of KoreaDepartment of Biochemistry Soonchunhyang University College of Medicine CheonanRepublic of KoreaDepartment of Biomedical Sciences Seoul National University College of Medicine SeoulRepublic of KoreaSL Bigen Inc. IncheonRepublic of KoreaSL Bigen Inc. IncheonRepublic of KoreaDepartment of Biomedical Sciences Seoul National University College of Medicine SeoulRepublic of KoreaDepartment of Life Sciences POSTECH PohangRepublic of KoreaDepartment of Life Sciences POSTECH PohangRepublic of KoreaSL Bigen Inc. IncheonRepublic of KoreaDepartment of Biomedical Sciences Seoul National University College of Medicine SeoulRepublic of KoreaSL Bigen Inc. IncheonRepublic of KoreaAbstract Despite the capability of extracellular vesicles (EVs) derived from Gram‐negative and Gram‐positive bacteria to induce potent anti‐tumour responses, large‐scale production of bacterial EVs remains as a hurdle for their development as novel cancer immunotherapeutic agents. Here, we developed manufacturing processes for mass production of Escherichia coli EVs, namely, outer membrane vesicles (OMVs). By combining metal precipitation and size‐exclusion chromatography, we isolated 357 mg in total protein amount of E. coli OMVs, which was equivalent to 3.93 × 1015 particles (1.10 × 1010 particles/μg in total protein amounts of OMVs) from 160 L of the conditioned medium. We show that these mass‐produced E. coli OMVs led to complete remission of two mouse syngeneic tumour models. Further analysis of tumour microenvironment in neoantigen‐expressing tumour models revealed that E. coli OMV treatment causes increased infiltration and activation of CD8+ T cells, especially those of cancer antigen‐specific CD8+ T cells with high expression of TCF‐1 and PD‐1. Furthermore, E. coli OMVs showed synergistic anti‐tumour activity with anti‐PD‐1 antibody immunotherapy, inducing substantial tumour growth inhibition and infiltration of activated cancer antigen‐specific stem‐like CD8+ T cells into the tumour microenvironment. These data highlight the potent anti‐tumour activities of mass‐produced E. coli OMVs as a novel candidate for developing next‐generation cancer immunotherapeutic agents.https://doi.org/10.1002/jev2.12357bacterial extracellular vesiclescombination immunotherapyimmunotherapeutic agentslarge‐scale mass productionouter membrane vesicles |
| spellingShingle | Solchan Won Changjin Lee Seoyoon Bae Jaemin Lee Dongsic Choi Min‐Gang Kim Sunghyun Song Jaewook Lee Eunhye Kim HaYoung Shin Anita Basukala Tae Ryong Lee Dong‐Sup Lee Yong Song Gho Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1 Journal of Extracellular Vesicles bacterial extracellular vesicles combination immunotherapy immunotherapeutic agents large‐scale mass production outer membrane vesicles |
| title | Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1 |
| title_full | Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1 |
| title_fullStr | Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1 |
| title_full_unstemmed | Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1 |
| title_short | Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1 |
| title_sort | mass produced gram negative bacterial outer membrane vesicles activate cancer antigen specific stem like cd8 t cells which enables an effective combination immunotherapy with anti pd 1 |
| topic | bacterial extracellular vesicles combination immunotherapy immunotherapeutic agents large‐scale mass production outer membrane vesicles |
| url | https://doi.org/10.1002/jev2.12357 |
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