Immunization with glypican-3 nanovaccine containing TLR7 agonist prevents the development of carcinogen-induced precancerous hepatic lesions to cancer in a murine model
文献类型：期刊论文
| 作者 | Ma, Yifan; Chen, Kun; Wu, Zhiyuan; Zang, Mengya; Wang, Ce; Wang, Yanmei; Wang, Dongmei; Qu, Chunfeng |
| 刊名 | AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
 |
| 出版日期 | 2018 |
| 文献子类 | 期刊论文 |
| 英文摘要 | Background: Glypican-3 (GPC3) is one of the key tissue markers that could discriminate malignant precancerous lesions from benign hepatic lesions in cirrhotic patients. We aimed to develop a GPC3 cancer vaccine to induce specific T cells to intervene in hepatocellular carcinoma (HCC) development. Methods: Synthesizing mannosylated liposomes (LPMan) as vaccine delivery system, incorporating one Toll-like receptor (TLR)-7/8 agonist CL097 as adjuvant, we prepared a GPC3 nanovaccine, LPMan-GPC3/CL097. We injected 25 mg/kg diethylnitrosamine intraperitoneally to induce autochthonous HCC in HBV-transgenic mice, which persistently express hepatitis B surface antigen in hepatocytes. Starting from week 8 after diethylnitrosamine injection when malignant hepatocytes generated, we immunized the mice subcutaneously every 2 weeks 4 times with LPMan-GPC3/CL097 containing 5 mu g of GPC3 plus 5 mu g of CL097. Results: The vaccine efficiently targeted draining lymph nodes where naive T cells reside and enhanced the expression of molecules involved in antigen presentation in migratory dendritic cells (DCs). Antigen was professionally processed in endoplasmic reticulum-Golgi system of DCs, subsequently priming both CD4(+) and CD8(+) T cells. The LPMan-GPC3/CL097 immunization generated significantly more GPC3-specific CD4(+) IFN gamma- and CD8(+) IFN gamma-producing T cells in mice spleens and livers, which specifically eliminated GPC3-expressing tumor cells. One week after last immunization (week 15 after diethylnitrosamine), 5/5 un-immunized, 5/5 sham (LPMan-CL097) and 1/5 LPMan-GPC3/CL097-immunized mice developed HCC. By week 20 after diethylnitrosamine, significantly less HCC developed in LPMan-GPC3/CL097-immunized mice than in sham-immunized mice (P<0.01). Conclusions: LPMan-GPC3/CL097 immunization induced de novo generation of specific T cells against tumor-associated antigen GPC3 that could prevent HCC development in cirrhotic liver. |
| URL标识 | 查看原文 |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/14868]  |
| 专题 | 深圳先进技术研究院_其他 |
| 推荐引用方式 GB/T 7714 | Ma, Yifan,Chen, Kun,Wu, Zhiyuan,et al. Immunization with glypican-3 nanovaccine containing TLR7 agonist prevents the development of carcinogen-induced precancerous hepatic lesions to cancer in a murine model[J]. AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH,2018. |
| APA | Ma, Yifan.,Chen, Kun.,Wu, Zhiyuan.,Zang, Mengya.,Wang, Ce.,...&Qu, Chunfeng.(2018).Immunization with glypican-3 nanovaccine containing TLR7 agonist prevents the development of carcinogen-induced precancerous hepatic lesions to cancer in a murine model.AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH. |
| MLA | Ma, Yifan,et al."Immunization with glypican-3 nanovaccine containing TLR7 agonist prevents the development of carcinogen-induced precancerous hepatic lesions to cancer in a murine model".AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH (2018). |
入库方式： OAI收割
来源：深圳先进技术研究院
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