Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis
Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) enginee...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Pedro Berraondo [verfasserIn] Ignacio Melero [verfasserIn] Jose Medina-Echeverz [verfasserIn] Alvaro Teijeira [verfasserIn] Fernando Aranda [verfasserIn] Maite Alvarez [verfasserIn] Assunta Cirella [verfasserIn] Maria Hinterberger [verfasserIn] Hubertus Hochrein [verfasserIn] Myriam Fernandez-Sendin [verfasserIn] Claudia Augusta Di Trani [verfasserIn] Celia Gomar [verfasserIn] Angela Bella [verfasserIn] Cigdem Atay [verfasserIn] Jose Gonzalez-Gomariz [verfasserIn] Irene Olivera [verfasserIn] Leire Arrizabalaga [verfasserIn] Joan Salvador Russo-Cabrera [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Übergeordnetes Werk: |
In: Journal for ImmunoTherapy of Cancer - BMJ Publishing Group, 2013, 11(2023), 11 |
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| Übergeordnetes Werk: |
volume:11 ; year:2023 ; number:11 |
| Links: |
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| DOI / URN: |
10.1136/jitc-2023-006702 |
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| Katalog-ID: |
DOAJ096913312 |
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| 245 | 1 | 0 | |a Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis |
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| 520 | |a Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. | ||
| 653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
| 700 | 0 | |a Ignacio Melero |e verfasserin |4 aut | |
| 700 | 0 | |a Jose Medina-Echeverz |e verfasserin |4 aut | |
| 700 | 0 | |a Alvaro Teijeira |e verfasserin |4 aut | |
| 700 | 0 | |a Fernando Aranda |e verfasserin |4 aut | |
| 700 | 0 | |a Maite Alvarez |e verfasserin |4 aut | |
| 700 | 0 | |a Assunta Cirella |e verfasserin |4 aut | |
| 700 | 0 | |a Maria Hinterberger |e verfasserin |4 aut | |
| 700 | 0 | |a Hubertus Hochrein |e verfasserin |4 aut | |
| 700 | 0 | |a Myriam Fernandez-Sendin |e verfasserin |4 aut | |
| 700 | 0 | |a Claudia Augusta Di Trani |e verfasserin |4 aut | |
| 700 | 0 | |a Celia Gomar |e verfasserin |4 aut | |
| 700 | 0 | |a Angela Bella |e verfasserin |4 aut | |
| 700 | 0 | |a Cigdem Atay |e verfasserin |4 aut | |
| 700 | 0 | |a Jose Gonzalez-Gomariz |e verfasserin |4 aut | |
| 700 | 0 | |a Irene Olivera |e verfasserin |4 aut | |
| 700 | 0 | |a Leire Arrizabalaga |e verfasserin |4 aut | |
| 700 | 0 | |a Joan Salvador Russo-Cabrera |e verfasserin |4 aut | |
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10.1136/jitc-2023-006702 doi (DE-627)DOAJ096913312 (DE-599)DOAJ602c6ffcbd964839b726a8c63461e54e DE-627 ger DE-627 rakwb eng RC254-282 Pedro Berraondo verfasserin aut Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ignacio Melero verfasserin aut Jose Medina-Echeverz verfasserin aut Alvaro Teijeira verfasserin aut Fernando Aranda verfasserin aut Maite Alvarez verfasserin aut Assunta Cirella verfasserin aut Maria Hinterberger verfasserin aut Hubertus Hochrein verfasserin aut Myriam Fernandez-Sendin verfasserin aut Claudia Augusta Di Trani verfasserin aut Celia Gomar verfasserin aut Angela Bella verfasserin aut Cigdem Atay verfasserin aut Jose Gonzalez-Gomariz verfasserin aut Irene Olivera verfasserin aut Leire Arrizabalaga verfasserin aut Joan Salvador Russo-Cabrera verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 11(2023), 11 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:11 year:2023 number:11 https://doi.org/10.1136/jitc-2023-006702 kostenfrei https://doaj.org/article/602c6ffcbd964839b726a8c63461e54e kostenfrei https://jitc.bmj.com/content/11/11/e006702.full kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 11 |
| spelling |
10.1136/jitc-2023-006702 doi (DE-627)DOAJ096913312 (DE-599)DOAJ602c6ffcbd964839b726a8c63461e54e DE-627 ger DE-627 rakwb eng RC254-282 Pedro Berraondo verfasserin aut Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ignacio Melero verfasserin aut Jose Medina-Echeverz verfasserin aut Alvaro Teijeira verfasserin aut Fernando Aranda verfasserin aut Maite Alvarez verfasserin aut Assunta Cirella verfasserin aut Maria Hinterberger verfasserin aut Hubertus Hochrein verfasserin aut Myriam Fernandez-Sendin verfasserin aut Claudia Augusta Di Trani verfasserin aut Celia Gomar verfasserin aut Angela Bella verfasserin aut Cigdem Atay verfasserin aut Jose Gonzalez-Gomariz verfasserin aut Irene Olivera verfasserin aut Leire Arrizabalaga verfasserin aut Joan Salvador Russo-Cabrera verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 11(2023), 11 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:11 year:2023 number:11 https://doi.org/10.1136/jitc-2023-006702 kostenfrei https://doaj.org/article/602c6ffcbd964839b726a8c63461e54e kostenfrei https://jitc.bmj.com/content/11/11/e006702.full kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 11 |
| allfields_unstemmed |
10.1136/jitc-2023-006702 doi (DE-627)DOAJ096913312 (DE-599)DOAJ602c6ffcbd964839b726a8c63461e54e DE-627 ger DE-627 rakwb eng RC254-282 Pedro Berraondo verfasserin aut Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ignacio Melero verfasserin aut Jose Medina-Echeverz verfasserin aut Alvaro Teijeira verfasserin aut Fernando Aranda verfasserin aut Maite Alvarez verfasserin aut Assunta Cirella verfasserin aut Maria Hinterberger verfasserin aut Hubertus Hochrein verfasserin aut Myriam Fernandez-Sendin verfasserin aut Claudia Augusta Di Trani verfasserin aut Celia Gomar verfasserin aut Angela Bella verfasserin aut Cigdem Atay verfasserin aut Jose Gonzalez-Gomariz verfasserin aut Irene Olivera verfasserin aut Leire Arrizabalaga verfasserin aut Joan Salvador Russo-Cabrera verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 11(2023), 11 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:11 year:2023 number:11 https://doi.org/10.1136/jitc-2023-006702 kostenfrei https://doaj.org/article/602c6ffcbd964839b726a8c63461e54e kostenfrei https://jitc.bmj.com/content/11/11/e006702.full kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 11 |
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10.1136/jitc-2023-006702 doi (DE-627)DOAJ096913312 (DE-599)DOAJ602c6ffcbd964839b726a8c63461e54e DE-627 ger DE-627 rakwb eng RC254-282 Pedro Berraondo verfasserin aut Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ignacio Melero verfasserin aut Jose Medina-Echeverz verfasserin aut Alvaro Teijeira verfasserin aut Fernando Aranda verfasserin aut Maite Alvarez verfasserin aut Assunta Cirella verfasserin aut Maria Hinterberger verfasserin aut Hubertus Hochrein verfasserin aut Myriam Fernandez-Sendin verfasserin aut Claudia Augusta Di Trani verfasserin aut Celia Gomar verfasserin aut Angela Bella verfasserin aut Cigdem Atay verfasserin aut Jose Gonzalez-Gomariz verfasserin aut Irene Olivera verfasserin aut Leire Arrizabalaga verfasserin aut Joan Salvador Russo-Cabrera verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 11(2023), 11 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:11 year:2023 number:11 https://doi.org/10.1136/jitc-2023-006702 kostenfrei https://doaj.org/article/602c6ffcbd964839b726a8c63461e54e kostenfrei https://jitc.bmj.com/content/11/11/e006702.full kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 11 |
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10.1136/jitc-2023-006702 doi (DE-627)DOAJ096913312 (DE-599)DOAJ602c6ffcbd964839b726a8c63461e54e DE-627 ger DE-627 rakwb eng RC254-282 Pedro Berraondo verfasserin aut Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ignacio Melero verfasserin aut Jose Medina-Echeverz verfasserin aut Alvaro Teijeira verfasserin aut Fernando Aranda verfasserin aut Maite Alvarez verfasserin aut Assunta Cirella verfasserin aut Maria Hinterberger verfasserin aut Hubertus Hochrein verfasserin aut Myriam Fernandez-Sendin verfasserin aut Claudia Augusta Di Trani verfasserin aut Celia Gomar verfasserin aut Angela Bella verfasserin aut Cigdem Atay verfasserin aut Jose Gonzalez-Gomariz verfasserin aut Irene Olivera verfasserin aut Leire Arrizabalaga verfasserin aut Joan Salvador Russo-Cabrera verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 11(2023), 11 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:11 year:2023 number:11 https://doi.org/10.1136/jitc-2023-006702 kostenfrei https://doaj.org/article/602c6ffcbd964839b726a8c63461e54e kostenfrei https://jitc.bmj.com/content/11/11/e006702.full kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 11 |
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Pedro Berraondo @@aut@@ Ignacio Melero @@aut@@ Jose Medina-Echeverz @@aut@@ Alvaro Teijeira @@aut@@ Fernando Aranda @@aut@@ Maite Alvarez @@aut@@ Assunta Cirella @@aut@@ Maria Hinterberger @@aut@@ Hubertus Hochrein @@aut@@ Myriam Fernandez-Sendin @@aut@@ Claudia Augusta Di Trani @@aut@@ Celia Gomar @@aut@@ Angela Bella @@aut@@ Cigdem Atay @@aut@@ Jose Gonzalez-Gomariz @@aut@@ Irene Olivera @@aut@@ Leire Arrizabalaga @@aut@@ Joan Salvador Russo-Cabrera @@aut@@ |
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In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. 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Pedro Berraondo |
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Pedro Berraondo misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis |
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RC254-282 Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis |
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Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis |
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Pedro Berraondo Ignacio Melero Jose Medina-Echeverz Alvaro Teijeira Fernando Aranda Maite Alvarez Assunta Cirella Maria Hinterberger Hubertus Hochrein Myriam Fernandez-Sendin Claudia Augusta Di Trani Celia Gomar Angela Bella Cigdem Atay Jose Gonzalez-Gomariz Irene Olivera Leire Arrizabalaga Joan Salvador Russo-Cabrera |
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intraperitoneal administration of a modified vaccinia virus ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis |
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Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis |
| abstract |
Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. |
| abstractGer |
Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. |
| abstract_unstemmed |
Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.Methods MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.Results Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+ T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.Conclusion Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity. |
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Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis |
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Ignacio Melero Jose Medina-Echeverz Alvaro Teijeira Fernando Aranda Maite Alvarez Assunta Cirella Maria Hinterberger Hubertus Hochrein Myriam Fernandez-Sendin Claudia Augusta Di Trani Celia Gomar Angela Bella Cigdem Atay Jose Gonzalez-Gomariz Irene Olivera Leire Arrizabalaga Joan Salvador Russo-Cabrera |
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7.400218 |