A novel human immune system mice model for assessing the immunogenicity of cancer vaccines
- VernacularTitle:评价肿瘤疫苗免疫原性的新型人免疫系统小鼠模型
- Author:
Liangliang JIANG
1
;
Tao JIANG
;
Jianhua LUO
;
Wenbing YAO
;
Hong TIAN
Author Information
1. 中国药科大学生命科学与技术学院，江苏省生物药物成药性研究重点实验室
- Publication Type:Journal Article
- Keywords:
human immune system mice;
model;
cancer vaccines;
autologous dendritic cells;
immunogenicity
- MeSH:
10.11665/j.issn.1000-5048.20190615
- From:
Journal of China Pharmaceutical University
2019;50(6):734-742
- CountryChina
- Language:Chinese
-
Abstract:
Human immune system(HIS)mice are usually used to evaluate the ability of tumor vaccines to induce cytotoxic T lymphocyte(CTL)effects, but they failed to accurately reflect the ability of cancer vaccines to induce humoral immune responses. In this study, human peripheral blood mononuclear cells were isolated by density gradient centrifugation and co-transplanted into NCG mice with in vitro differentiated dendritic cells(DCs)to establish a DC-HIS mouse model. In DC-HIS mice, co-transplanted antigen-presenting cells(HLA-DR+CD11c+)could colonize the spleen of model mice. Moreover, co-transplantation of DCs significantly increased the proportion of activated human CD4+ T/CD8+ T cells and B cells in HIS mice, indicating that DC-HIS mice could better mimic the human immune responses. The immunogenicity of the targeted HER2 protein vaccine(NitraTh-HER2)was evaluated using the DCs-HIS mice. The results showed that the NitraTh-HER2 vaccine was able to induce the production of HER2-specific human IgG antibodies with a significant antibody-dependent cell-mediated cytotoxicity(ADCC)effect and the lysis rate of target cell SK-BR-3 reached 47. 1%. The NitraTh-HER2 vaccine was able to produce antigen-specific CTL effect, and the lysis rate of target cell SK-BR-3 reached 14. 6%. Taken together, the DC-HIS mouse model provides an effective method for predicting the immunogenicity of human tumor vaccines.
