Glycosyl-phosphatidylinositol-anchored interleukin-2 expressed on tumor-derived exosomes induces antitumor immune response in vitro

Tumori. 2010 May-Jun;96(3):452-9. doi: 10.1177/030089161009600313.

Abstract

Aims and background: Tumor-derived exosomes (TEXs) have been considered as a new kind of cancer vaccine, but the antitumor effects are not satisfactory. In order to improve the efficacy of TEXs, we investigated whether exosomes derived from glycosyl-phosphatidylinositol-anchored interleukin 2 (GPI-IL-2) gene-modified bladder cancer cells can increase the antitumor effects.

Methods and study design: We transfected melanoma antigen-1 (MAGE-1)-expressing T24 tumor cells with a plasmid encoding GPI-IL-2 and prepared the TEXs. Exosomes expressing GPI-IL-2 were characterized by electron microscope and Western blot analysis.

Results: IL-2 was present on the cell surface in the GPI-anchored form as demonstrated by fluorescent microscope and ELISA analyses. Exosomes expressing GPI-IL-2 naturally contained bioactive GPI-IL-2 and tumor-associated antigen MAGE-1. Moreover, exosomes expressing GPI-IL-2-pulsed dendritic cells could induce the proliferation of T cells and the antigen-specific cytotoxic T-lymphocyte immune response more efficiently.

Conclusions: GPI-IL-2 gene-modified tumor cells can make the TEXs contain GPI-IL-2, resulting in increased antitumor effects. Our study provided a feasible approach for exosome-based tumor immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cancer Vaccines / immunology
  • Cell Proliferation / drug effects
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Exosomes / genetics
  • Exosomes / immunology*
  • Exosomes / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glycosylphosphatidylinositols / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Microscopy, Electron
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / metabolism

Substances

  • Cancer Vaccines
  • Glycosylphosphatidylinositols
  • Interleukin-2
  • Interferon-gamma