Preparation and antitumor effects of nanovaccines with MAGE-3 peptides in transplanted gastric cancer in mice / 癌症

ABSTRACT

<p><b>BACKGROUND AND OBJECTIVE</b>As 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.</p><p><b>METHODS</b>We 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.</p><p><b>RESULTS</b>We 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%.</p><p><b>CONCLUSIONS</b>MAGE-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.</p>