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Tumor Biology

, Volume 37, Issue 4, pp 5305–5316 | Cite as

Tagging staphylococcal enterotoxin B (SEB) with TGFaL3 for breast cancer therapy

  • Forough Yousefi
  • Seyed Davar Siadat
  • Alireza Azizi Saraji
  • Saeed Hesaraki
  • Mohammad Mehdi Aslani
  • Seyed Fazlollah Mousavi
  • Abbas Ali Imani Fooladi
Original Article

Abstract

Recent research has attempted to direct superantigens towards tumors by means of tumor-targeted superantigen (TTS) strategy. In this study, we explored the antitumor property of TTS by fusing the third loop of transforming growth factor α (TGFαL3) to staphylococcal enterotoxin type B (SEB) and investigated the possibility of the therapeutic application of TGFαL3-SEB as a novel antitumor candidate in mice bearing breast cancer. Treatment was performed through intratumoral and intravenous injection of TGFαL3-SEB. Tumor size/volume, long-term survival, and cytokine secretion were assessed. In addition, the toxicity of each treatment on liver and kidneys was examined. Our results indicated that the relative tumor volume significantly increased in the mice receiving intratumoral TGFaL3-SEB (p < 0.05). Surprisingly, 5 out of the 14 mice were cleared from the tumor thoroughly in 10–25 days after intratumoral administration of TGFaL3-SEB. Quantification of cytokines clearly showed that the mice receiving intratumoral SEB significantly secreted higher interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) compared with the other groups (p < 0.05). The antitumor effect was followed by inhibition of cell proliferation (Ki-67) and micro vascularization (CD31). The highest and lowest levels of tumor necrosis were observed in the intratumoral administration of TGFαL3-SEB (85 %) and PBS (14 %), respectively. Intratumoral injection of TGFαL3-SEB increased the lifespan of the mice so 37.5 % of them could survive for more than 6 months (p < 0.05). Overall, our findings indicated that intratumoral administration of TGFαL3-SEB effectively inhibited the growth of breast tumors through induction of necrosis and suppressing proliferation and angiogenesis without systemic toxicity.

Keywords

Breast cancer Immunotherapy Staphylococcal enterotoxin type B Transforming growth factor α 

Notes

Acknowledgments

This study was financially supported by the Pasteur Institute of Iran (Ph.D Grant No. B-8804).

Consent for publication

All of the animal experiments were carried out under a project license issued by the Pasteur Institute of Iran according to the local Animal Experimentation Rules.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Forough Yousefi
    • 1
  • Seyed Davar Siadat
    • 1
  • Alireza Azizi Saraji
    • 2
  • Saeed Hesaraki
    • 3
  • Mohammad Mehdi Aslani
    • 1
  • Seyed Fazlollah Mousavi
    • 1
  • Abbas Ali Imani Fooladi
    • 4
  1. 1.Department of BacteriologyPasteur Institute of IranTehranIran
  2. 2.Department of Medical Virology, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
  3. 3.Department of Pathobiology, Science and Research BranchIslamic Azad UniversityTehranIran
  4. 4.Applied Microbiology Research CenterBaqiyatallah University of Medical SciencesTehranIran

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