Induction of protective anti-CTL epitope responses against HER-2-positive breast cancer based on multivalent T7 phage nanoparticles

PLoS One. 2012;7(11):e49539. doi: 10.1371/journal.pone.0049539. Epub 2012 Nov 15.

Abstract

We report here the development of multivalent T7 bacteriophage nanoparticles displaying an immunodominant H-2k(d)-restricted CTL epitope derived from the rat HER2/neu oncoprotein. The immunotherapeutic potential of the chimeric T7 nanoparticles as anti-cancer vaccine was investigated in BALB/c mice in an implantable breast tumor model. The results showed that T7 phage nanoparticles confer a high immunogenicity to the HER-2-derived minimal CTL epitope, as shown by inducing robust CTL responses. Furthermore, the chimeric nanoparticles protected mice against HER-2-positive tumor challenge in both prophylactic and therapeutic setting. In conclusion, these results suggest that CTL epitope-carrying T7 phage nanoparticles might be a promising approach for development of T cell epitope-based cancer vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Bacteriophage T7 / chemistry
  • Bacteriophage T7 / immunology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Capsid Proteins / immunology
  • Cell Line
  • Cell Surface Display Techniques
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lipopolysaccharides / genetics
  • Lipopolysaccharides / immunology
  • Mice
  • Molecular Sequence Data
  • Nanoparticles* / chemistry
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / immunology
  • Protein Binding / immunology
  • Rats
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Monoclonal
  • Cancer Vaccines
  • Capsid Proteins
  • Epitopes, T-Lymphocyte
  • Immunoglobulin G
  • Lipopolysaccharides
  • Peptides
  • Recombinant Fusion Proteins
  • Interleukin-4
  • Interferon-gamma
  • Receptor, ErbB-2

Grants and funding

This study was part of a PhD thesis supported by Tarbiat Modares University and Shahid Beheshti University of Medical Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.