Synergistic effects between Staphylococcal enterotoxin type B and Monophosphoryl lipid A against mouse fibrosarcoma.
OBJECTIVE
Staphylococcal enterotoxin B (SEB) is a potent inducer of cytotoxic T-cell activity, cytokine production and necrosis induction in vivo. Monophosphoryl lipid A (MPL) is an adjuvant derived from the lipopolysaccharide of E. coli, Salmonella Minnesota Re595 and other gram negative bacteria. We investigated the possibility of the therapeutic application of SEB+ MPL in mice with fibrosarcoma.


METHODS
The antitumor effect of SEB+MPL, SEB and MPL in mice with inoculated fibrosarcoma tumor (WEHI-164) was examined by intravenous (i.v.) and intratumoral (i.t.) injection and the sizes of the inoculated tumors, IFN-gamma production, and CD4(+)/CD8(+) T cell infiltration were determined. The inoculated tumors were also examined histologically.


RESULTS
In the i.v.-injected group of mice with SEB+ MPL, reduction of tumor size showed a significant difference compared with mice in the i.t., the i.v. (MPL)-injected groups and the negative control group (p < 0.02). Moreover, the mice in the i.v. (SEB+ MPL)-injected group showed significantly higher levels of IFN-gamma (p < 0.009) and CD4(+)/CD8(+) T cell infiltration when compared with the other groups (p < 0.02). A significantly higher frequency of necrosis in tumor tissues was also observed in mice in the i.v. (SEB+ MPL)-injected group in comparison with other groups (p < 0.009).


CONCLUSIONS
Our findings suggest that tumor cell death is caused by increased cytotoxic T-cell activity, cytokine levels, in response to IV injection of SEB+MPL. They also suggest that tumor cell death by synergistic effect of one of the strongest bacterial superantigens (SEB) with monophosphoryl lipid A and SEB+MPL may be a good option for use as a novel therapy in patients with fibrosarcoma.
Imani Fooladi
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Research Centers of Molecular Biology, Baqiyatallah University of Medical Sciences, Tehran, 3456-445, Iran. imanifouladi.a@gmail.com
Sattari
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Reza Nourani
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D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D004768:Enterotoxins / Q000627:therapeutic use*; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D018089:Superantigens / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology
D000276:Adjuvants, Immunologic; D004768:Enterotoxins; D007376:Interleukin-2; D008050:Lipid A; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; C048436:monophosphoryl lipid A