title: Staphylococcal enterotoxin B/texosomes as a candidate for breast cancer immunotherapy.
abstract: A new recombinant construct made up of two components, texosomes (TEX) and staphylococcal enterotoxin B (SEB), showed cytostatic properties against several types of tumor cells in vitro. Here, we aimed to assess the construct's antitumor immunogenicity in a murine tumor model. SEB was anchored onto purified texosomes and was used for immunization of mice before challenge with 4T1 cells. Tumor size, survival time, necrosis, metastasis rate, and the levels of IL-2, IL-4, IL-17, IL-12, TNF-α, and IFN-γ were measured. Immunization of the mice with TEX-SEB increased the stimulation index of splenocytes significantly compared with the PBS-treated mice (p < 0.01). In addition, there was a significant increase of TNF-α, IL-2, and IFN-γ secreted from isolated splenocytes of the mice immunized by either TEX-SEB, TEX + SEB, TEX, or SEB in comparison with PBS (p < 0.001, p < 0.001, and p < 0.05, respectively), whereas no significant change of IL-4 secretion was observed in any treated groups. Finding from tumor tissue homogenate testing showed that the level of IL-17 and IFN-γ among mice immunized with TEX-SEB was significantly lower than PBS-treated group (p < 0.05). IL-12, IL-4, and TNF-α levels were not significantly different from PBS- and TEX-SEB-immunized groups except in the SEB-immunized mice. Although TEX-SEB immunization relatively prolonged the survival of the mice, it had no inhibitory impact on tumor size. Pathologic manifestations showed the significant rise of necrosis after immunization with TEX-SEB compared to PBS (p < 0.01). Overall, our findings suggest that the presence of SEB rescues tumorigenesis effects of TEX making the construct an appropriate candidate for tumor immunotherapy.
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas Ali
authors.initials: AA
authors.lastname: Imani Fooladi
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Halabian
authors.affiliation: Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amin
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. hosseini361@yahoo.com.
authors.forename: Hamideh
authors.initials: H
authors.lastname: Mahmoodzadeh Hosseini
mesh_terms: D000818:Animals; D001706:Biopsy; D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018089:Superantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D004768:Enterotoxins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal
keywords: Breast cancer; Exosome display; Immunotherapy; Staphylococcal entorotoxin B; Texosome