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

被引:3
作者
Qi, Yuan [1 ,2 ]
Xing, Kailin [1 ,2 ]
Zhang, Lanlin [1 ,2 ]
Zhao, Fangyu [3 ]
Yao, Ming [3 ]
Hu, Aiqun [3 ]
Wu, Xianghua [1 ,2 ]
机构
[1] Fudan Univ, Dept Med Oncol, Shanghai Canc Ctr, 270 Dong An Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst,Renji Hosp, 25 Ln2200 Xietu Rd, Shanghai 200032, Peoples R China
关键词
Cancer; Measles vaccine; Hemagglutinin; Cancer immunotherapy; Cytotoxic T lymphocytes; TUMOR MICROENVIRONMENT; SUPPRESSOR-CELLS; T-CELLS; RESPONSES; THERAPY; RECEPTOR; CD4(+); CD46;
D O I
10.1007/s00432-018-2720-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. 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. Active vaccination using measles vaccine not only protected mice from developing tumors, but also eradicated established tumors. Measles vaccine elicited H-specific IFN-gamma, TNF-alpha 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). 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.
引用
收藏
页码:1945 / 1957
页数:13
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