Oncolytic Measles Virus Encoding Interleukin-12 Mediated Antitumor Activity and Immunologic Control of Colon Cancer In Vivo and Ex Vivo
- PMID: 32783751
- DOI: 10.1089/cbr.2019.3084
Oncolytic Measles Virus Encoding Interleukin-12 Mediated Antitumor Activity and Immunologic Control of Colon Cancer In Vivo and Ex Vivo
Abstract
Background: An oncolytic measles virus encoding interleukin 12 (IL-12) to treat colon cancer in vivo and ex vivo to investigate its effect on the viability and apoptosis of colon cancer cells in this study. Materials and Methods: A rat model was established to evaluate the immunostimulatory capabilities and therapeutic efficacy of vectors encoding an IL-12 fusion protein (MeVac FmIL-12 vectors). TUNEL staining, Western blot, and enzyme-linked immunosorbent assay were performed to examine the impacts of MeVac FmIL-12 on the expression of inflammatory cytokines. Cell transfection was carried out to validate the anti-tumor role of MeVac FmIL-12 in vitro. Flow cytometry and MTT assay were performed to assess the effects of MeVac FmIL-12 on cell apoptosis and viability. Result: High concentrations (10-1000 ng/mL) of murine IL-12 fusion protein (FmIL-12) decreased the production of interferon γ (IFN-γ) in a concentration-dependent manner and reflected FmIL-12-induced overstimulation. Rats treated with MeVac vectors encoding FmIL-12 showed a significantly increased level of FmIL-12 overtime and a concentration-dependent (0.01-10 ng/mL) increase in IFN-γ production. MeVac FmIL-12 also increased the expression of inflammatory cytokines (IFN-γ, tumor necrosis factor α, and IL-6) both in vivo and in vitro. MeVac FmIL-12 promoted cell apoptosis and reduced cell viability, which helped to trigger a systemic anti-tumor immune response, both in vivo and in vitro. Conclusion: In this study, we suggested that MeVac FmIL-12 enhanced the therapeutic efficacy of tumor treatment by improving anti-tumor immunity.
Keywords: IFN-γ; IL-12; TNF-α; colon cancer; immunotherapy; inflammation; oncolytic measles virus.
Comment in
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Re: "Oncolytic Measles Virus Encoding Interleukin-12 Mediated Antitumor Activity and Immunologic Control of Colon Cancer In Vivo and Ex Vivo" by Wang et al.Cancer Biother Radiopharm. 2021 Feb;36(1):106-107. doi: 10.1089/cbr.2020.4566. Epub 2020 Dec 1. Cancer Biother Radiopharm. 2021. PMID: 33259718 No abstract available.
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