Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models
Previous studies have shown that local delivery of tumor antigen-specific CD8+ T lymphocytes engineered to transiently express single-chain IL-12 mRNA is highly efficacious. Peritoneal dissemination of cancer is a frequent and often fatal patient condition usually diagnosed when the tumor burden is...
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2147317 |
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| author | Claudia Augusta Di Trani Assunta Cirella Leire Arrizabalaga Ángela Bella Myriam Fernandez-Sendin Joan Salvador Russo-Cabrera Celia Gomar Irene Olivera Elizabeth Bolaños José González-Gomariz Maite Álvarez Iñaki Etxeberria Belen Palencia Álvaro Teijeira Ignacio Melero Pedro Berraondo Fernando Aranda |
| author_facet | Claudia Augusta Di Trani Assunta Cirella Leire Arrizabalaga Ángela Bella Myriam Fernandez-Sendin Joan Salvador Russo-Cabrera Celia Gomar Irene Olivera Elizabeth Bolaños José González-Gomariz Maite Álvarez Iñaki Etxeberria Belen Palencia Álvaro Teijeira Ignacio Melero Pedro Berraondo Fernando Aranda |
| author_sort | Claudia Augusta Di Trani |
| collection | DOAJ |
| description | Previous studies have shown that local delivery of tumor antigen-specific CD8+ T lymphocytes engineered to transiently express single-chain IL-12 mRNA is highly efficacious. Peritoneal dissemination of cancer is a frequent and often fatal patient condition usually diagnosed when the tumor burden is too large and hence uncontrollable with current treatment options. In this study, we have modeled intracavitary adoptive T cell therapy with OVA-specific OT-I T cells electroporated with IL-12 mRNA to treat B16-OVA and PANC02-OVA tumor spread in the peritoneal cavity. Tumor localization in the omentum and the effects of local T-cell encounter with the tumor antigens were monitored, the gene expression profile evaluated, and the phenotypic reprogramming of several immune subsets was characterized. Intraperitoneal administration of T cells promoted homing to the omentum more effectively than intravenous administration. Transient IL-12 expression was responsible for a favorable reprogramming of the tumor immune microenvironment, longer persistence of transferred T lymphocytes in vivo, and the development of immunity to endogenous antigens following primary tumor eradication. The efficacy of the strategy was at least in part recapitulated with the adoptive transfer of lower affinity transgenic TCR-bearing PMEL-1 T lymphocytes to treat the aggressive intraperitoneally disseminated B16-F10 tumor. Locoregional adoptive transfer of transiently IL-12-armored T cells appears to offer promising therapeutic advantages in terms of anti-tumor efficacy to treat peritoneal carcinomatosis. |
| format | Article |
| id | doaj-art-7995ddacfe9f449ca1ff8dccf0f9a256 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-7995ddacfe9f449ca1ff8dccf0f9a2562025-08-20T02:50:44ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2022.2147317Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse modelsClaudia Augusta Di Trani0Assunta Cirella1Leire Arrizabalaga2Ángela Bella3Myriam Fernandez-Sendin4Joan Salvador Russo-Cabrera5Celia Gomar6Irene Olivera7Elizabeth Bolaños8José González-Gomariz9Maite Álvarez10Iñaki Etxeberria11Belen Palencia12Álvaro Teijeira13Ignacio Melero14Pedro Berraondo15Fernando Aranda16Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainPrevious studies have shown that local delivery of tumor antigen-specific CD8+ T lymphocytes engineered to transiently express single-chain IL-12 mRNA is highly efficacious. Peritoneal dissemination of cancer is a frequent and often fatal patient condition usually diagnosed when the tumor burden is too large and hence uncontrollable with current treatment options. In this study, we have modeled intracavitary adoptive T cell therapy with OVA-specific OT-I T cells electroporated with IL-12 mRNA to treat B16-OVA and PANC02-OVA tumor spread in the peritoneal cavity. Tumor localization in the omentum and the effects of local T-cell encounter with the tumor antigens were monitored, the gene expression profile evaluated, and the phenotypic reprogramming of several immune subsets was characterized. Intraperitoneal administration of T cells promoted homing to the omentum more effectively than intravenous administration. Transient IL-12 expression was responsible for a favorable reprogramming of the tumor immune microenvironment, longer persistence of transferred T lymphocytes in vivo, and the development of immunity to endogenous antigens following primary tumor eradication. The efficacy of the strategy was at least in part recapitulated with the adoptive transfer of lower affinity transgenic TCR-bearing PMEL-1 T lymphocytes to treat the aggressive intraperitoneally disseminated B16-F10 tumor. Locoregional adoptive transfer of transiently IL-12-armored T cells appears to offer promising therapeutic advantages in terms of anti-tumor efficacy to treat peritoneal carcinomatosis.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2147317Peritoneal carcinomatosisinterleukin 12adoptive cell transfermRNAlocoregional treatment |
| spellingShingle | Claudia Augusta Di Trani Assunta Cirella Leire Arrizabalaga Ángela Bella Myriam Fernandez-Sendin Joan Salvador Russo-Cabrera Celia Gomar Irene Olivera Elizabeth Bolaños José González-Gomariz Maite Álvarez Iñaki Etxeberria Belen Palencia Álvaro Teijeira Ignacio Melero Pedro Berraondo Fernando Aranda Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models OncoImmunology Peritoneal carcinomatosis interleukin 12 adoptive cell transfer mRNA locoregional treatment |
| title | Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models |
| title_full | Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models |
| title_fullStr | Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models |
| title_full_unstemmed | Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models |
| title_short | Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models |
| title_sort | intracavitary adoptive transfer of il 12 mrna engineered tumor specific cd8 t cells eradicates peritoneal metastases in mouse models |
| topic | Peritoneal carcinomatosis interleukin 12 adoptive cell transfer mRNA locoregional treatment |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2147317 |
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