Oncolytic newcastle disease virus delivered by mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment

Keshavarz, M ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.1186/s12985-020-01326-w
  3. Publisher: BioMed Central Ltd , 2020
  4. Abstract:
  5. Background: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME). Results: Our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 9) and increased infiltration of tumor microenvironment with CD11b + myeloid and Gr1 + MDSCs cells. Conclusions: Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and apoptosis in the tumor microenvironment. © 2020 The Author(s)
  6. Keywords:
  7. CD8 + ; Human papillomavirus ; Mesenchymal stem cells ; Myeloid-derived suppressor cells ; Oncolytic Newcastle disease virus ; Caspase 3 ; Caspase 9 ; CD11b antigen ; Gamma interferon ; Interleukin 12 ; Interleukin 4 ; Animal cell ; Animal experiment ; Animal tissue ; Apoptosis ; C57BL 6 mouse ; cancer immunotherapy ; CD8+ T lymphocyte ; Cell differentiation ; Cell engineering ; Cell infiltration ; Concentration (parameter) ; Controlled study ; Cytokine release ; Cytolysis ; Cytotoxicity ; Female ; Flow cytometry ; Histopathology ; Immune response ; Immunohistochemistry ; In vitro study ; Lymphocyte proliferation ; Malignant neoplasm ; Mesenchymal stem cell ; Mouse ; Myeloid-derived suppressor cell ; Newcastle disease virus ; Nonhuman ; Oncolytic virotherapy ; Papillomavirus infection ; Splenic T cell ; Therapy effect ; Tropism ; Tumor growth ; Tumor microenvironment ; Tumor volume ; Upregulation
  8. Source: Virology Journal ; Volume 17, Issue 1 , 2020
  9. URL: https://virologyj.biomedcentral.com/articles/10.1186/s12985-020-01326-w