Glycosyl-phosphatidylinositol-anchored interleukin-2 expressed on tumor-derived exosomes induces antitumor immune response in vitro.
OBJECTIVE
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
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.
Zhang
Jiamo
J
Department of Urology The First Affiliated Hospital, Chongqing Medical University, China.
Zhang
Yao
Y
Luo
Chunli
C
Xia
Yuguo
Y
Chen
Honglin
H
Wu
Xiaohou
X
D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D055354:Exosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008854:Microscopy, Electron; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000378:metabolism
D019496:Cancer Vaccines; D017261:Glycosylphosphatidylinositols; D007376:Interleukin-2; D007371:Interferon-gamma