The utility of poly(γ-glutamic acid) nanoparticles as antigen delivery carriers in dendritic cell-based cancer immunotherapy

Biol Pharm Bull. 2010;33(12):2003-7. doi: 10.1248/bpb.33.2003.

Abstract

Cytotoxic T-lymphocytes (CTLs) specific for tumor-associated antigens (TAAs) act in the immune surveillance system as major effector cells to eliminate malignant cells. Immunization with TAA-loaded dendritic cells (DCs) has great potential for treating cancer, because DCs are potent antigen-presenting cells capable of inducing antigen-specific CTLs by the primary activation of naive T-lymphocytes. The establishment of a non-cytotoxic and efficient antigen delivery method is required to improve the efficacy of DC-based cancer immunotherapy. We developed biodegradable poly(γ-glutamic acid) nanoparticles (γ-PGA NPs) that can efficiently entrap various proteins as antigen delivery carriers. γ-PGA NPs efficiently delivered entrapped antigenic proteins into DCs without cytotoxicity and presented antigens to DCs via major histocompatibility complex class I and II molecules. Immunization with TAA-loaded DCs using γ-PGA NPs inhibited tumor growth by inducing TAA-specific CTLs. These findings indicate that γ-PGA NPs can function as useful antigen delivery carriers in DC-based cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / administration & dosage*
  • Dendritic Cells*
  • Drug Carriers*
  • Female
  • Immunotherapy*
  • Lymphocyte Activation*
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Polyglutamic Acid / analogs & derivatives*
  • T-Lymphocytes / metabolism

Substances

  • Antigens
  • Drug Carriers
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid