Staphylococcal enterotoxin B as DNA vaccine against breast cancer in a murine model

被引:2
|
作者
Halabian, Raheleh [1 ]
Jahangiri, Abolfazl [1 ]
Sedighian, Hamid [1 ]
Behzadi, Elham [2 ]
Fooladi, Abbas Ali Imani [1 ]
机构
[1] Baqiyatallah Univ Med Sci, Syst Biol & Poisonings Inst, Appl Microbiol Res Ctr, Tehran, Iran
[2] Acad Med Sci IR Iran, Tehran, Iran
关键词
SEB; Immunotherapy; DNA vaccine; Breast cancer; Anti-tumor immunity; IN-SILICO ANALYSES; MAMMARY-TUMOR; IMMUNOTHERAPY;
D O I
10.1007/s10123-023-00348-y
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Recently, many efforts have been made to treat cancer using recombinant bacterial toxins and this strategy has been used in clinical trials of various cancers. Therapeutic DNA cancer vaccines are now considered as a promising strategy to activate the immune system against cancer. Cancer vaccines could induce specific and long-lasting immune responses against tumors. This study aimed to evaluate the antitumor potency of the SEB DNA vaccine as a new antitumor candidate against breast tumors in vivo. To determine the effect of the SEB construct on inhibiting tumor cell growth in vivo, the synthetic SEB gene, subsequent codon optimization, and embedding the cleavage sites were sub-cloned to an expression vector. Then, SEB construct, SEB, and PBS were injected into the mice. After being vaccinated, 4T1 cancer cells were injected subcutaneously into the right flank of mice. Then, the cytokine levels of IL-4 and IFN-gamma were estimated by the ELISA method to evaluate the antitumor activity. The spleen lymphocyte proliferation, tumor size, and survival time were assessed. The concentration of IFN-gamma in the SEB-Vac group showed a significant increase compared to other groups. The production of IL-4 in the group that received the DNA vaccine did not change significantly compared to the control group. The lymphocyte proliferation increased significantly in the mice group that received SEB construct than PBS control group (p < 0.001). While there was a meaningful decrease in tumor size (p < 0.001), a significant increase in tumor tissue necrosis (p < 0.01) and also in survival time of the animal model receiving the recombinant construct was observed. The designed SEB gene construct can be a new model vaccine for breast cancer because it effectively induces necrosis and produces specific immune responses. This structure does not hurt normal cells and is a safer treatment than chemotherapy and radiation therapy. Its slow and long-term release gently stimulates the immune system and cellular memory. It could be applied as a new model for inducing apoptosis and antitumor immunity to treat cancer.
引用
收藏
页码:939 / 949
页数:11
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