Preparation and antitumor effects of nanovaccines with MAGE-3 peptides in transplanted gastric cancer in mice.
- Author:
Jun YANG
1
;
Zhi-Hua LI
;
Jia-Jia ZHOU
;
Ru-Fu CHEN
;
Liang-Zheng CHENG
;
Quan-Bo ZHOU
;
Li-Qun YANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antigens, Neoplasm; chemistry; immunology; Cancer Vaccines; administration & dosage; Cell Line, Tumor; Chitosan; chemistry; Dendritic Cells; immunology; Deoxycholic Acid; chemistry; Drug Carriers; chemistry; Epitopes, T-Lymphocyte; immunology; Male; Mice; Nanoparticles; Neoplasm Proteins; chemistry; immunology; Neoplasm Transplantation; Stomach Neoplasms; pathology; therapy; T-Lymphocytes, Cytotoxic; immunology; Tumor Burden
- From:Chinese Journal of Cancer 2010;29(4):359-364
- CountryChina
- Language:English
-
Abstract:
BACKGROUND AND OBJECTIVEAs a prospective vaccine carrier, nanoparticles can protect antigens from degradation and enhance immune response. This study prepared nanovaccines with MAGE-3-derived CD4+-CD8+T cell epitope peptides, and investigated its character and antitumor effects on transplanted gastric cancer in mice.
METHODSWe adopted the self-assembly method to prepare peptide/chitosan conjugated with deoxycholic acid (chitosan-deoxycholic acid) nanoparticles. We observed the appearance of the chitosan-deoxycholic acidnanoparticles through a transmission electron microscope (TEM) and analyzed the peptide content and its release pattern by fluorescence spectrophotometry. We observed tumor-suppression efficacy in vivo through animal experiments.
RESULTSWe successfully prepared nanoparticles with MAGE-3 peptide antigen, and its encapsulation efficiency and loading level were about 37% and 17.0%, respectively. These nanoparticles presented a delayed release pattern in phosphate buffered saline (PBS) at pH 7.4, and the full release time was about 48 h. In 2 mg/mL lysozyme, the nanoparticles showed a sudden release, and the full release time was about 24 h. ELISPOT and cytotoxic experiments showed that the MAGE-3 peptide loaded nanoparticles could stimulate immune response in vivo and could generate MAGE-3-targeted cytotoxic T lymphocytes (CTLs), and kill MAGE-3-specific tumor cells. Tumor suppression experiments showed that the regression ratio of the peptide-loaded nanoparticles group was 37.81%.
CONCLUSIONSMAGE-3 peptide/chitosan-deoxycholic acidvaccine-loaded nanoparticles can stimulate antitumor immune response in vivo and can regress the growth of mouse forestomach carcinoma cell line MFC.