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

Yunshan Yang, Fangming Xiu, Zhijian Cai, Jianli Wang, Qingqing Wang, Yangxin Fu, Xuetao Cao

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)389-399
Number of pages11
JournalJournal of Cancer Research and Clinical Oncology
Volume133
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

Exosomes
Interleukin-2
Genes
Neoplasms
Cancer Vaccines
Ovalbumin
Vaccination
T-Lymphocytes
Ultracentrifugation
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Centrifugation
Inbred C57BL Mouse
Natural Killer Cells
Sucrose
Western Blotting

Keywords

  • Cancer vaccine
  • CTL
  • Exosomes
  • Immunotherapy
  • Interleukin-2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells. / Yang, Yunshan; Xiu, Fangming; Cai, Zhijian; Wang, Jianli; Wang, Qingqing; Fu, Yangxin; Cao, Xuetao.

In: Journal of Cancer Research and Clinical Oncology, Vol. 133, No. 6, 01.06.2007, p. 389-399.

Research output: Contribution to journalArticle

Yang, Yunshan ; Xiu, Fangming ; Cai, Zhijian ; Wang, Jianli ; Wang, Qingqing ; Fu, Yangxin ; Cao, Xuetao. / Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells. In: Journal of Cancer Research and Clinical Oncology. 2007 ; Vol. 133, No. 6. pp. 389-399.
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