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

Chin J Cancer. 2010 Apr;29(4):359-64. doi: 10.5732/cjc.009.10541.

Abstract

Background and objective: 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.

Methods: 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.

Results: 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%.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / 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
  • Neoplasm Proteins / immunology*
  • Neoplasm Transplantation
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Burden

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Drug Carriers
  • Epitopes, T-Lymphocyte
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Deoxycholic Acid
  • Chitosan