Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery

Biomaterials. 2011 May;32(14):3666-78. doi: 10.1016/j.biomaterials.2011.01.067. Epub 2011 Feb 23.


Nanotechnology-based antigen delivery has been developing as a vaccine strategy due to its dose-sparing and prolonged antigen presentation features. In the current study, we examined the feasibility of nanoparticle (NP)-mediated delivery of antigenic peptides to efficiently induce cytotoxic T lymphocyte responses against tumor-associated self-antigens in C57BL/6 mouse models. The biodegradable poly(D,L-lactide-co-glycolide) nanoparticle (PLGA-NP) carrying murine melanoma antigenic peptides, hgp100(25-33) and TRP2(180-188), were prepared by double emulsion method. Efficient uptake of PLGA-NP by murine dendritic cells was shown in vitro and in vivo, using NP labeled with the fluorescent dye DiD. Intradermal injection of peptide-loaded PLGA-NP into mice induced antigen-specific T cell responses more strongly than the peptides mixed with Freund's adjuvant. More importantly, vaccination with PLGA-NP carrying both TRP2(180-188) and a toll-like receptor 4 agonist, monophosphoryl lipid A, significantly delayed growth of subcutaneously inoculated B16 melanoma cells in a prophylactic setting. Furthermore, the anti-tumor activity of NP-mediated peptide vaccination was significantly augmented by combined treatment with interferon-γ, which might prevent tumor escape through up-regulation of MHC class I expression on tumor cells. Our findings demonstrate the feasibility of NP-mediated antigen delivery for cancer immunotherapy, in particular when immune escape mechanisms of tumor cells are blocked simultaneously.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens / chemistry
  • Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Lactic Acid / chemistry*
  • Mass Spectrometry
  • Mice
  • Nanoparticles / chemistry*
  • Peptides / chemistry
  • Peptides / immunology*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tandem Mass Spectrometry


  • Antibodies, Monoclonal
  • Antigens
  • Peptides
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid