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

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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.

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Abbreviations

CTL:

Cytotoxic T lymphocytes

DC:

Dendritic cells

DEX:

DC-derived exosomes

Exo:

Conventional exosomes

Exo/IL-2:

IL-2-containing exosomes

HSP:

Heat shock protein

IFN-γ:

Interferin-γ

IL-2:

Interleukin 2

MHC:

Major histocompatibility complex

OVA:

Ovalbumin

TEX:

Tumor-derived exosomes

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (30328011, 30490240, 30121002) and the National Key Basic Research Program of China (2001CB510002).

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Authors and Affiliations

  1. Institute of Immunology, Zhejiang University, Zhejiang, Hangzhou, 310031, People’s Republic of China

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

  2. Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, 800 Xiang Yin Road, Shanghai, 200433, People’s Republic of China

    Yunshan Yang & Xuetao Cao

Authors
  1. Yunshan Yang
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  2. Fangming Xiu
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  3. Zhijian Cai
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  4. Jianli Wang
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  5. Qingqing Wang
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  6. Yangxin Fu
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  7. Xuetao Cao
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Corresponding author

Correspondence to Xuetao Cao.

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The first two authors contributed equally to this work.

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Yang, Y., Xiu, F., Cai, Z. et al. Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells. J Cancer Res Clin Oncol 133, 389–399 (2007). https://doi.org/10.1007/s00432-006-0184-7

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  • DOI: https://doi.org/10.1007/s00432-006-0184-7

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