Nanoparticles built by self-assembly of amphiphilic gamma-PGA can deliver antigens to antigen-presenting cells with high efficiency: a new tumor-vaccine carrier for eliciting effector T cells

Vaccine. 2008 Mar 4;26(10):1303-13. doi: 10.1016/j.vaccine.2007.12.037. Epub 2008 Jan 15.

Abstract

Nanotechnology is a fundamental technology for designing and generating innovative carriers for biomacromolecular drugs. Biodegradable poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent vaccine carriers capable of delivering antigenic proteins to antigen-presenting cells (APCs) and eliciting potent immune responses based on antigen-specific cytotoxic T lymphocytes. In mice, subcutaneous immunization with gamma-PGA NPs entrapping ovalbumin (OVA) more effectively inhibited the growth of OVA-transfected tumors than immunization with OVA emulsified using Freund's complete adjuvant. In addition, gamma-PGA NPs did not induce histopathologic changes after subcutaneous injection or acute toxicity through intravenous injection. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins into APCs, and these antigen-capturing APCs migrated to regional lymph nodes. Our results demonstrate that a gamma-PGA NP system for antigen delivery will advance the clinical utility of vaccines against cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigens, Neoplasm / administration & dosage*
  • Antigens, Neoplasm / adverse effects
  • Antigens, Neoplasm / chemistry
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Drug Carriers
  • Freund's Adjuvant / pharmacology
  • Immunohistochemistry
  • Immunotherapy
  • Inflammation / chemically induced
  • Inflammation / pathology
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Neoplasm Transplantation / immunology
  • Ovalbumin / immunology
  • Polyglutamic Acid / adverse effects
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / chemistry
  • Polyglutamic Acid / pharmacology
  • Reproducibility of Results
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Drug Carriers
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid
  • Ovalbumin
  • Freund's Adjuvant