title: Tagging staphylococcal enterotoxin B (SEB) with TGFaL3 for breast cancer therapy.
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.
authors.affiliation: Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Forough
authors.initials: F
authors.lastname: Yousefi
authors.affiliation: Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Seyed Davar
authors.initials: SD
authors.lastname: Siadat
authors.affiliation: Department of Medical Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Alireza Azizi
authors.initials: AA
authors.lastname: Saraji
authors.affiliation: Department of Pathobiology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Hesaraki
authors.affiliation: Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Aslani
authors.affiliation: Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran. mousavi@pasteur.ac.ir.
authors.forename: Seyed Fazlollah
authors.initials: SF
authors.lastname: Mousavi
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. imanifouladi.a@gmail.com.
authors.forename: Abbas Ali
authors.initials: AA
authors.lastname: Imani Fooladi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects*; D004768:Enterotoxins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy*; D015514:Oncogene Proteins, Fusion; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D004768:Enterotoxins; D015514:Oncogene Proteins, Fusion; D018089:Superantigens; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma
keywords: Breast cancer; Immunotherapy; Staphylococcal enterotoxin type B; Transforming growth factor α