Systemic delivery of TNF-armed myxoma virus plus immune checkpoint inhibitor eliminates lung metastatic mouse osteosarcoma
| العنوان: | Systemic delivery of TNF-armed myxoma virus plus immune checkpoint inhibitor eliminates lung metastatic mouse osteosarcoma |
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| المؤلفون: | Kenneth M Lowe, Joseph N. Blattman, Masmudur M. Rahman, Jazmin Galvan Achi, Nancy Y. Villa, Lina S. Franco, Ana Lemos de Matos, Hannah Canter, Joshua Carmen, Natalie M. Elliott, Jacquelyn Kilbourne, Nicole Appel, Evelyn Luna, Grant McFadden, John D. Christie |
| المصدر: | Molecular Therapy Oncolytics Molecular Therapy: Oncolytics, Vol 22, Iss, Pp 539-554 (2021) |
| بيانات النشر: | American Society of Gene & Cell Therapy, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, bone marrow, Myxoma virus, Virus, immune checkpoint inhibitors, Immune system, myxoma virus, osteosarcoma, medicine, Pharmacology (medical), Virotherapy, RC254-282, ICI, biology, business.industry, armed oncolytic virus, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, biology.organism_classification, K7M2, Oncolytic virus, medicine.anatomical_structure, carrier cells, Oncology, PBMCs, Cancer research, Systemic administration, Molecular Medicine, Osteosarcoma, Original Article, Bone marrow, business, TNF-alpha |
| الوصف: | Solid cancers that metastasize to the lungs represent a major therapeutic challenge. Current treatment paradigms for lung metastases consist of radiation therapy, chemotherapies, and surgical resection, but there is no single treatment or combination that is effective for all tumor types. To address this, oncolytic myxoma virus (MYXV) engineered to express human tumor necrosis factor (vMyx-hTNF) was tested after systemic administration in an immunocompetent mouse K7M2-Luc lung metastatic osteosarcoma model. Virus therapy efficacy against pre-seeded lung metastases was assessed after systemic infusion of either naked virus or ex vivo-loaded autologous bone marrow leukocytes or peripheral blood mononuclear cells (PBMCs). Results of this study showed that the PBMC pre-loaded strategy was the most effective at reducing tumor burden and increasing median survival time, but sequential intravenous multi-dosing with naked virus was comparably effective to a single infusion of PBMC-loaded virus. PBMC-loaded vMyx-hTNF also potentially synergized very effectively with immune checkpoint inhibitors anti-PD-1, anti-PD-L1, and anti-cytotoxic T lymphocyte associated protein 4 (CTLA-4). Finally, in addition to the pro-immune stimulation caused by unarmed MYXV, the TNF transgene of vMyx-hTNF further induced the unique expression of numerous additional cytokines associated with the innate and adaptive immune responses in this model. We conclude that systemic ex vivo virotherapy with TNF-α-armed MYXV represents a new potential strategy against lung metastatic cancers like osteosarcoma and can potentially act synergistically with established checkpoint immunotherapies. Graphical abstract How to deliver and specific arming of oncolytic viruses are two of the biggest questions currently facing the field of oncolytic virotherapy. In this study, leukocytes are used to deliver TNF-α-armed myxoma virus to lung metastatic osteosarcoma tumors. The efficacy of these modalities is shown alone and in combination with immune checkpoint inhibitors. |
| اللغة: | English |
| تدمد: | 2372-7705 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d45fd2a0e250abd190d13e37276899a http://europepmc.org/articles/PMC8433070 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3d45fd2a0e250abd190d13e37276899a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23727705 |
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