AI Article Synopsis
- Glypican-3 (GPC3) is a tissue marker useful for differentiating between malignant and benign liver lesions in cirrhotic patients, prompting the development of a GPC3-based cancer vaccine aimed at reducing the risk of hepatocellular carcinoma (HCC).
- The research involved creating a nanovaccine (LPMan-GPC3/CL097) that combines GPC3 and a TLR agonist, which was administered to HBV-transgenic mice to stimulate immune response against HCC.
- Results showed that the vaccine effectively increased GPC3-specific T cells capable of targeting and eliminating tumor cells, significantly reducing HCC incidence in treated mice compared to controls.
Article Abstract
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 µg of GPC3 plus 5 µg of CL097.
Results: The vaccine efficiently targeted draining lymph nodes where naïve 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 IFNγ- and CD8 IFNγ-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 (<0.01).
Conclusions: LPMan-GPC3/CL097 immunization induced generation of specific T cells against tumor-associated antigen GPC3 that could prevent HCC development in cirrhotic liver.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038065 | PMC |
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