Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity

Vaccine. 2008 Sep 15;26(39):5046-57. doi: 10.1016/j.vaccine.2008.07.035. Epub 2008 Aug 3.


The purpose of this study was to evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA)-based vaccines in breaking immunotolerance to cancer-associated self-antigens. Vaccination of mice bearing melanoma B16 tumors with PLGA nanoparticles (NP) co-encapsulating the poorly immunogenic melanoma antigen, tyrosinase-related protein 2 (TRP2), along with Toll-like receptor (TLR) ligand (7-acyl lipid A) was examined. Remarkably, this vaccine was able to induce therapeutic anti-tumor effect. Activated TRP2-specific CD8 T cells were capable of interferon (IFN)-gamma secretion at lymph nodes and spleens of the vaccinated mice. More importantly, TRP2/7-acyl lipid A-NP treated group has shown immunostimulatory milieu at the tumor microenvironment, as evidenced by increased level of pro-inflammatory cytokines compared to control group. These results support the potential use of PLGA nanoparticles as competent carriers for future cancer vaccine formulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic / immunology
  • Drug Carriers / therapeutic use
  • Interferon-gamma / immunology
  • Intramolecular Oxidoreductases / immunology
  • Lactic Acid / administration & dosage
  • Lactic Acid / therapeutic use*
  • Lipid A / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage
  • Nanoparticles / therapeutic use
  • Polyglycolic Acid / administration & dosage
  • Polyglycolic Acid / therapeutic use*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Toll-Like Receptor 4 / immunology*


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Drug Carriers
  • Lipid A
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Interferon-gamma
  • Intramolecular Oxidoreductases
  • dopachrome isomerase