Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors
Abstract Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic can...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42668-7 |
| _version_ | 1797636754579128320 |
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| author | Jacopo Chiaro Gabriella Antignani Sara Feola Michaela Feodoroff Beatriz Martins Hanne Cojoc Salvatore Russo Manlio Fusciello Firas Hamdan Valentina Ferrari Daniele Ciampi Ilkka Ilonen Jari Räsänen Mikko Mäyränpää Jukka Partanen Satu Koskela Jarno Honkanen Jussi Halonen Lukasz Kuryk Maria Rescigno Mikaela Grönholm Rui M. Branca Janne Lehtiö Vincenzo Cerullo |
| author_facet | Jacopo Chiaro Gabriella Antignani Sara Feola Michaela Feodoroff Beatriz Martins Hanne Cojoc Salvatore Russo Manlio Fusciello Firas Hamdan Valentina Ferrari Daniele Ciampi Ilkka Ilonen Jari Räsänen Mikko Mäyränpää Jukka Partanen Satu Koskela Jarno Honkanen Jussi Halonen Lukasz Kuryk Maria Rescigno Mikaela Grönholm Rui M. Branca Janne Lehtiö Vincenzo Cerullo |
| author_sort | Jacopo Chiaro |
| collection | DOAJ |
| description | Abstract Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic cancer vaccination. To date, research on mesothelioma has focused on the identification of molecular signatures to better classify and characterize the disease, and little is known about therapeutic targets that engage cytotoxic (CD8+) T cells. In this study we investigate the immunopeptidomic antigen-presented landscape of MPM in both murine (AB12 cell line) and human cell lines (H28, MSTO-211H, H2452, and JL1), as well as in patients’ primary tumors. Applying state-of-the-art immuno-affinity purification methodologies, we identify MHC I-restricted peptides presented on the surface of malignant cells. We characterize in vitro the immunogenicity profile of the eluted peptides using T cells from human healthy donors and cancer patients. Furthermore, we use the most promising peptides to formulate an oncolytic virus-based precision immunotherapy (PeptiCRAd) and test its efficacy in a mouse model of mesothelioma in female mice. Overall, we demonstrate that the use of immunopeptidomic analysis in combination with oncolytic immunotherapy represents a feasible and effective strategy to tackle untreatable tumors. |
| first_indexed | 2024-03-11T12:39:39Z |
| format | Article |
| id | doaj.art-6e1ca484af774f7185adf7528cf6e262 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T12:39:39Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6e1ca484af774f7185adf7528cf6e2622023-11-05T12:24:07ZengNature PortfolioNature Communications2041-17232023-11-0114111610.1038/s41467-023-42668-7Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumorsJacopo Chiaro0Gabriella Antignani1Sara Feola2Michaela Feodoroff3Beatriz Martins4Hanne Cojoc5Salvatore Russo6Manlio Fusciello7Firas Hamdan8Valentina Ferrari9Daniele Ciampi10Ilkka Ilonen11Jari Räsänen12Mikko Mäyränpää13Jukka Partanen14Satu Koskela15Jarno Honkanen16Jussi Halonen17Lukasz Kuryk18Maria Rescigno19Mikaela Grönholm20Rui M. Branca21Janne Lehtiö22Vincenzo Cerullo23Drug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiValo Therapeutics OyDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiDepartment of Biomedical Sciences, Humanitas UniversityDepartment of Biomedical Sciences, Humanitas UniversityDepartment of General Thoracic and Esophageal Surgery, Heart and Lung Center, Helsinki University HospitalDepartment of General Thoracic and Esophageal Surgery, Heart and Lung Center, Helsinki University HospitalDepartment of Pathology, Helsinki University HospitalResearch & Development Finnish Red Cross Blood Service HelsinkiFinnish Red Cross Blood Service BiobankFinnish Red Cross Blood Service BiobankFinnish Red Cross Blood Service BiobankValo Therapeutics OyDepartment of Biomedical Sciences, Humanitas UniversityDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiScience for Life Laboratory, Department of Oncology-Pathology, Karolinska InstitutetScience for Life Laboratory, Department of Oncology-Pathology, Karolinska InstitutetDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of HelsinkiAbstract Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic cancer vaccination. To date, research on mesothelioma has focused on the identification of molecular signatures to better classify and characterize the disease, and little is known about therapeutic targets that engage cytotoxic (CD8+) T cells. In this study we investigate the immunopeptidomic antigen-presented landscape of MPM in both murine (AB12 cell line) and human cell lines (H28, MSTO-211H, H2452, and JL1), as well as in patients’ primary tumors. Applying state-of-the-art immuno-affinity purification methodologies, we identify MHC I-restricted peptides presented on the surface of malignant cells. We characterize in vitro the immunogenicity profile of the eluted peptides using T cells from human healthy donors and cancer patients. Furthermore, we use the most promising peptides to formulate an oncolytic virus-based precision immunotherapy (PeptiCRAd) and test its efficacy in a mouse model of mesothelioma in female mice. Overall, we demonstrate that the use of immunopeptidomic analysis in combination with oncolytic immunotherapy represents a feasible and effective strategy to tackle untreatable tumors.https://doi.org/10.1038/s41467-023-42668-7 |
| spellingShingle | Jacopo Chiaro Gabriella Antignani Sara Feola Michaela Feodoroff Beatriz Martins Hanne Cojoc Salvatore Russo Manlio Fusciello Firas Hamdan Valentina Ferrari Daniele Ciampi Ilkka Ilonen Jari Räsänen Mikko Mäyränpää Jukka Partanen Satu Koskela Jarno Honkanen Jussi Halonen Lukasz Kuryk Maria Rescigno Mikaela Grönholm Rui M. Branca Janne Lehtiö Vincenzo Cerullo Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors Nature Communications |
| title | Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors |
| title_full | Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors |
| title_fullStr | Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors |
| title_full_unstemmed | Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors |
| title_short | Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors |
| title_sort | development of mesothelioma specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors |
| url | https://doi.org/10.1038/s41467-023-42668-7 |
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