Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model
IntroductionMalignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy...
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Frontiers Media S.A.
2023-11-01
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| author | Mariangela Garofalo Magdalena Wieczorek Ines Anders Monika Staniszewska Michal Lazniewski Michal Lazniewski Marta Prygiel Aleksandra Anna Zasada Teresa Szczepińska Dariusz Plewczynski Dariusz Plewczynski Stefano Salmaso Paolo Caliceti Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Ramon Alemany Beate Rinner Katarzyna Pancer Lukasz Kuryk Lukasz Kuryk Lukasz Kuryk |
| author_facet | Mariangela Garofalo Magdalena Wieczorek Ines Anders Monika Staniszewska Michal Lazniewski Michal Lazniewski Marta Prygiel Aleksandra Anna Zasada Teresa Szczepińska Dariusz Plewczynski Dariusz Plewczynski Stefano Salmaso Paolo Caliceti Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Ramon Alemany Beate Rinner Katarzyna Pancer Lukasz Kuryk Lukasz Kuryk Lukasz Kuryk |
| author_sort | Mariangela Garofalo |
| collection | DOAJ |
| description | IntroductionMalignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic vector, with an anti-PD-1 monoclonal antibody.MethodsThe efficacy of the vector was confirmed in vitro in three mesothelioma cell lines – H226, Mero-82, and MSTO-211H, and subsequently the antineoplastic properties in combination with anti-PD-1 was evaluated in xenograft H226 mesothelioma BALB/c and humanized NSG mouse models.Results and discussionAnticancer efficacy was attributed to reduced tumour volume and increased infiltration of tumour infiltrating lymphocytes, including activated cytotoxic T-cells (GrB+CD8+). Additionally, a correlation between tumour volume and activated CD8+ tumour infiltrating lymphocytes was observed. These findings were confirmed by transcriptomic analysis carried out on resected human tumour tissue, which also revealed upregulation of CD83 and CRTAM, as well as several chemokines (CXCL3, CXCL9, CXCL11) in the tumour microenvironment. Furthermore, according to observations, the combinatorial therapy had the strongest effect on reducing mesothelin and MUC16 levels. Gene set enrichment analysis suggested that the combinatorial therapy induced changes to the expression of genes belonging to the “adaptive immune response” gene ontology category. Combinatorial therapy with oncolytic adenovirus with checkpoint inhibitors may improve anticancer efficacy and survival by targeted cancer cell destruction and triggering of immunogenic cell death. Obtained results support further assessment of the AdV5/3-D24-ICOSL-CD40L in combination with checkpoint inhibitors as a novel therapeutic perspective for mesothelioma treatment. |
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| language | English |
| last_indexed | 2024-03-10T18:06:13Z |
| publishDate | 2023-11-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-7aa8e45e1b514cb0a739223e07f1bcad2023-11-20T08:27:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-11-011310.3389/fonc.2023.12593141259314Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse modelMariangela Garofalo0Magdalena Wieczorek1Ines Anders2Monika Staniszewska3Michal Lazniewski4Michal Lazniewski5Marta Prygiel6Aleksandra Anna Zasada7Teresa Szczepińska8Dariusz Plewczynski9Dariusz Plewczynski10Stefano Salmaso11Paolo Caliceti12Vincenzo Cerullo13Vincenzo Cerullo14Vincenzo Cerullo15Vincenzo Cerullo16Vincenzo Cerullo17Ramon Alemany18Beate Rinner19Katarzyna Pancer20Lukasz Kuryk21Lukasz Kuryk22Lukasz Kuryk23Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, ItalyDepartment of Virology, National Institute of Public Health, National Institute of Hygiene (NIH) - National Research Institute, Warsaw, PolandDivision of Biomedical Research, Medical University of Graz, Graz, AustriaCentre for Advanced Materials and Technologies, Warsaw University of Technology, Warsaw, PolandCentre for Advanced Materials and Technologies, Warsaw University of Technology, Warsaw, PolandDepartment of Bacteriology and Biocontamination Control, National Institute of Public Health, National Institute of Hygiene (NIH) - National Research Institute, Warsaw, PolandDepartament of Sera and Vaccines Evaluation, National Institute of Public Health, National Institute of Hygiene (NIH) - National Research Institute, Warsaw, PolandDepartament of Sera and Vaccines Evaluation, National Institute of Public Health, National Institute of Hygiene (NIH) - National Research Institute, Warsaw, PolandCentre for Advanced Materials and Technologies, Warsaw University of Technology, Warsaw, PolandLaboratory of Bioinformatics and Computational Genomics, Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, PolandLaboratory of Functional and Structural Genomics, Centre of New Technologies, University of Warsaw, Warsaw, PolandDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, ItalyDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, ItalyDrug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland0Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland1Translational Immunology Program (TRIMM), Faculty of Medicine Helsinki University, University of Helsinki, Helsinki, Finland2Digital Precision Cancer Medicine Flagship (iCAN), University of Helsinki, Helsinki, Finland3Department of Molecular Medicine and Medical Biotechnology and CEINGE, Naples University Federico II, Naples, Italy4Oncobell Program of Bellvitge Biomedical Research Institute (IDIBELL), ProCure Program of Catalan Institute of Oncology (ICO), Avinguda de la Granvia de l’Hospitalet, L'Hospitalet de Llobrega, Barcelona, SpainDivision of Biomedical Research, Medical University of Graz, Graz, AustriaDepartment of Virology, National Institute of Public Health, National Institute of Hygiene (NIH) - National Research Institute, Warsaw, PolandDepartment of Virology, National Institute of Public Health, National Institute of Hygiene (NIH) - National Research Institute, Warsaw, PolandCentre for Advanced Materials and Technologies, Warsaw University of Technology, Warsaw, Poland5Clinical Science, Valo Therapeutics, Helsinki, FinlandIntroductionMalignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic vector, with an anti-PD-1 monoclonal antibody.MethodsThe efficacy of the vector was confirmed in vitro in three mesothelioma cell lines – H226, Mero-82, and MSTO-211H, and subsequently the antineoplastic properties in combination with anti-PD-1 was evaluated in xenograft H226 mesothelioma BALB/c and humanized NSG mouse models.Results and discussionAnticancer efficacy was attributed to reduced tumour volume and increased infiltration of tumour infiltrating lymphocytes, including activated cytotoxic T-cells (GrB+CD8+). Additionally, a correlation between tumour volume and activated CD8+ tumour infiltrating lymphocytes was observed. These findings were confirmed by transcriptomic analysis carried out on resected human tumour tissue, which also revealed upregulation of CD83 and CRTAM, as well as several chemokines (CXCL3, CXCL9, CXCL11) in the tumour microenvironment. Furthermore, according to observations, the combinatorial therapy had the strongest effect on reducing mesothelin and MUC16 levels. Gene set enrichment analysis suggested that the combinatorial therapy induced changes to the expression of genes belonging to the “adaptive immune response” gene ontology category. Combinatorial therapy with oncolytic adenovirus with checkpoint inhibitors may improve anticancer efficacy and survival by targeted cancer cell destruction and triggering of immunogenic cell death. Obtained results support further assessment of the AdV5/3-D24-ICOSL-CD40L in combination with checkpoint inhibitors as a novel therapeutic perspective for mesothelioma treatment.https://www.frontiersin.org/articles/10.3389/fonc.2023.1259314/fullimmune checkpoint inhibitorsimmunotherapyoncolytic adenovirusmesotheliomaanti PD-1TILs |
| spellingShingle | Mariangela Garofalo Magdalena Wieczorek Ines Anders Monika Staniszewska Michal Lazniewski Michal Lazniewski Marta Prygiel Aleksandra Anna Zasada Teresa Szczepińska Dariusz Plewczynski Dariusz Plewczynski Stefano Salmaso Paolo Caliceti Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Vincenzo Cerullo Ramon Alemany Beate Rinner Katarzyna Pancer Lukasz Kuryk Lukasz Kuryk Lukasz Kuryk Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model Frontiers in Oncology immune checkpoint inhibitors immunotherapy oncolytic adenovirus mesothelioma anti PD-1 TILs |
| title | Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model |
| title_full | Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model |
| title_fullStr | Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model |
| title_full_unstemmed | Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model |
| title_short | Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model |
| title_sort | novel combinatorial therapy of oncolytic adenovirus adv5 3 d24 icosl cd40l with anti pd 1 exhibits enhanced anti cancer efficacy through promotion of intratumoral t cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model |
| topic | immune checkpoint inhibitors immunotherapy oncolytic adenovirus mesothelioma anti PD-1 TILs |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1259314/full |
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