title: Enhanced presentation of MHC class Ia, Ib and class II-restricted peptides encapsulated in biodegradable nanoparticles: a promising strategy for tumor immunotherapy.
abstract: BACKGROUND
  Many peptide-based cancer vaccines have been tested in clinical trials with a limited success, mostly due to difficulties associated with peptide stability and delivery, resulting in inefficient antigen presentation. Therefore, the development of suitable and efficient vaccine carrier systems remains a major challenge.
  
  
  METHODS
  To address this issue, we have engineered polylactic-co-glycolic acid (PLGA) nanoparticles incorporating: (i) two MHC class I-restricted clinically-relevant peptides, (ii) a MHC class II-binding peptide, and (iii) a non-classical MHC class I-binding peptide. We formulated the nanoparticles utilizing a double emulsion-solvent evaporation technique and characterized their surface morphology, size, zeta potential and peptide content. We also loaded human and murine dendritic cells (DC) with the peptide-containing nanoparticles and determined their ability to present the encapsulated peptide antigens and to induce tumor-specific cytotoxic T lymphocytes (CTL) in vitro.
  
  
  RESULTS
  We confirmed that the nanoparticles are not toxic to either mouse or human dendritic cells, and do not have any effect on the DC maturation. We also demonstrated a significantly enhanced presentation of the encapsulated peptides upon internalization of the nanoparticles by DC, and confirmed that the improved peptide presentation is actually associated with more efficient generation of peptide-specific CTL and T helper cell responses.
  
  
  CONCLUSIONS
  Encapsulating antigens in PLGA nanoparticles offers unique advantages such as higher efficiency of antigen loading, prolonged presentation of the antigens, prevention of peptide degradation, specific targeting of antigens to antigen presenting cells, improved shelf life of the antigens, and easy scale up for pharmaceutical production. Therefore, these findings are highly significant to the development of synthetic vaccines, and the induction of CTL for adoptive immunotherapy.
authors: Moores UCSD Cancer Center, University of California San Diego, CA, USA. wma@ucsd.edu
authors: Wenxue
authors: W
authors: Ma
authors: Trevor
authors: T
authors: Smith
authors: Vladimir
authors: V
authors: Bogin
authors: Yu
authors: Y
authors: Zhang
authors: Cengiz
authors: C
authors: Ozkan
authors: Mihri
authors: M
authors: Ozkan
authors: Melanie
authors: M
authors: Hayden
authors: Stephanie
authors: S
authors: Schroter
authors: Ewa
authors: E
authors: Carrier
authors: Davorka
authors: D
authors: Messmer
authors: Vipin
authors: V
authors: Kumar
authors: Boris
authors: B
authors: Minev
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001673:Biodegradation, Environmental; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D004705:Endocytosis; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D055767:Immobilized Proteins / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010455:Peptides / Q000276:immunology*; D010641:Phenotype; D011100:Polyglycolic Acid / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D055767:Immobilized Proteins; D010455:Peptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid