Protective immunity elicited by measles vaccine exerts anti-tumor effects on measles virus hemagglutinin gene-modified cancer cells in a mouse model

麻疹疫苗诱导的保护性免疫在小鼠模型中对麻疹病毒血凝素基因修饰的癌细胞具有抗肿瘤作用

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作者:Yuan Qi ,Kailin Xing ,Lanlin Zhang ,Fangyu Zhao ,Ming Yao ,Aiqun Hu ,Xianghua Wu

Abstract

Purpose: Measles vaccine is widely used in China to prevent the measles virus (MV) infection. People immunized with measles vaccine can obtain long-term protective immunity. Measles virus surface glycoprotein hemagglutinin (H) can also induce MV-specific immune responses. However, little is known about whether the existence of the protective immune system against MV in the host can exert anti-tumor effects and whether the MV-H gene can serve as a therapeutic gene. Methods: We first vaccinated mice with measles vaccine, then inoculated them with MV-H protein-expressing tumor cells and observed the rate of tumor formation. We also treated mice with H protein-expressing tumor cells with measles vaccine and assessed tumor size and overall survival. Results: Active vaccination using measles vaccine not only protected mice from developing tumors, but also eradicated established tumors. Measles vaccine elicited H-specific IFN-γ, TNF-α and granzyme B-producing CD8+ T cells and increased cytotoxic T lymphocyte (CTL) activity specific for H antigen, which provided a strong therapeutic benefit against H protein-expressing tumors. In addition, measles vaccine decreased the population of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). Conclusions: Our study demonstrated that tumor cells expressing H protein could activate the immune memory response against MV, which exerted specific anti-tumor effects, and indicated that the MV-H gene can be used as a potential therapeutic gene for cancer gene therapy.

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