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

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.

• Authors: Jiamo Zhang, Yao Zhang, Chunli Luo, Yuguo Xia, Honglin Chen, Xiaohou Wu
• Journal: Tumori (Tumori) 2010 May-Jun Vol. 96 Issue 3 Pg. 452-9 ISSN: 0300-8916 [Print] United States
• PMID: 20845808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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