Article

Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells.

Institute of Immunology, Zhejiang University, Zhejiang, Hangzhou 310031, People's Republic of China.
Journal of Cancer Research and Clinical Oncology (impact factor: 2.56). 07/2007; 133(6):389-99. DOI:10.1007/s00432-006-0184-7
Source: PubMed

ABSTRACT Tumor-derived exosomes (TEX) have been proposed as a new kind of cancer vaccine; however, their in vivo antitumor effects are not satisfactory. In order to further improve the efficacy of vaccination with TEX, we investigated whether interleukin-2 (IL-2) genetic modification of tumor cells can make IL-2 presence in the exosomes, thus increasing antitumor effects of the TEX.
E.G7-OVA tumor cells expressing Ovalbumin (OVA) as a tumor model antigen were used to prepare TEX by serial centrifugation and sucrose gradients ultracentrifugation. To demonstrate their antitumor effects, IL-2-containing exosomes (Exo/IL-2) were injected subcutaneously into C57BL/C mice: either bearing tumor or followed by tumor inoculation.
We found IL-2 within those exosomes as detected by both ELISA and Western blot. Vaccination with these Exo/IL-2 could induce antigen-specific Th1-polarized immune response and Cytotoxic T lymphocytes (CTL) more efficiently, resulting in more significant inhibition of tumor growth. CD8(+) T cells are the main effector cells, however, CD4(+) T cells, and NK cells are also involved in the induction of antitumor response of this approach.
Our results demonstrate that IL-2 genetic modification of tumor cells can make the TEX contain IL-2 with the increased antitumor effects, representing a promising way of exosome-based tumor vaccine.

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Keywords

antitumor effects
 
antitumor response
 
bearing tumor
 
cancer vaccine
 
Cytotoxic T lymphocytes
 
E.G7-OVA tumor cells
 
exosome-based tumor vaccine
 
IL-2 genetic modification
 
IL-2-containing exosomes
 
increased antitumor effects
 
main effector cells
 
new kind
 
promising way
 
significant inhibition
 
sucrose gradients ultracentrifugation
 
tumor inoculation
 
tumor model antigen
 
Tumor-derived exosomes
 
vivo antitumor effects
 
Western blot