RAFTsomes containing epitope-MHC-II complexes mediated CD4+ T cell activation and antigen-specific immune responses

Pharm Res. 2013 Jan;30(1):60-9. doi: 10.1007/s11095-012-0849-7. Epub 2012 Aug 10.

Abstract

Purpose: To develop a liposome formulation incorporating antigen-presenting cells (APCs) membrane microdomains with enriched epitope/MHC complexes to evaluate the activities of these liposomes (RAFTsomes) to activate T cells and prime immune responses.

Methods: We isolated membrane microdomain structures that contained the epitope/MHC complexes from ovalbumin (OVA) primed dendritic cells (DCs), and reconstituted them on liposomes surface by detergent dialysis. The resulted RAFTsomes were purified by density gradient centrifugation. Their T cell activation functions were evaluated by IL-2 secreting and proliferation assays in vitro. In vivo immune responses and the protective effect against OVA expressing EG.7 tumor challenge were also examined.

Results: Membrane microdomains containing enriched epitope/MHC complexes can be reconstituted into liposomes with defined size and composition. The integrity and activities of these complexes after reconstitution were confirmed by in vitro T cell assays. OVA epitope loaded RAFTsomes injected in vivo resulted in high anti-OVA IgG production (predominantly IgG1). The immunized mice were protected from EG.7 tumor cell inoculation challenge.

Conclusions: Based on these findings, we propose that RAFTsomes can be prepared with unique properties that may be used as an antigen delivery system for immunotherapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Cells, Cultured
  • Dendritic Cells / chemistry
  • Dendritic Cells / immunology*
  • Epitopes / chemistry
  • Epitopes / immunology
  • Epitopes / therapeutic use*
  • Genes, MHC Class II*
  • Interleukin-2 / immunology
  • Liposomes / chemistry
  • Liposomes / immunology*
  • Lymphocyte Activation*
  • Membrane Microdomains / chemistry
  • Membrane Microdomains / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / immunology
  • Neoplasms / prevention & control*
  • Ovalbumin / immunology

Substances

  • Cancer Vaccines
  • Epitopes
  • Interleukin-2
  • Liposomes
  • Ovalbumin