Staphylococcal enterotoxin B as DNA vaccine against breast cancer in a murine model
Raheleh Halabian1, Abolfazl Jahangiri1, Hamid Sedighian1
1Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Abstract:
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-γ 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-γ 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.
Insights
A novel DNA cancer vaccine using the SEB construct shows significant promise for treating breast cancer. This vaccine effectively stimulates immune responses, reduces tumor size, and increases survival time in preclinical models.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Recombinant bacterial toxins and DNA cancer vaccines are emerging strategies for cancer treatment.
- Cancer vaccines aim to elicit specific, long-lasting immune responses against tumors.
- Current treatments like chemotherapy and radiation therapy have limitations and side effects.
Purpose of the Study:
- To evaluate the antitumor efficacy of a novel Staphylococcal Enterotoxin B (SEB) DNA vaccine against breast tumors in vivo.
- To assess the SEB DNA vaccine's ability to induce specific immune responses and inhibit tumor growth.
Main Methods:
- A synthetic SEB gene was codon-optimized and cloned into an expression vector.
- Mice were vaccinated with the SEB construct, SEB alone, or a phosphate-buffered saline (PBS) control.
- 4T1 breast cancer cells were implanted, and antitumor activity was assessed by measuring cytokine levels (IL-4, IFN-γ), lymphocyte proliferation, tumor size, necrosis, and survival.
Main Results:
- The SEB DNA vaccine significantly increased Interferon-gamma (IFN-γ) levels and spleen lymphocyte proliferation compared to controls.
- Significant reductions in tumor size and notable increases in tumor tissue necrosis were observed in the SEB-vaccinated group.
- The SEB DNA vaccine significantly improved the survival time of the tumor-bearing mice.
Conclusions:
- The designed SEB DNA gene construct serves as a promising new vaccine model for breast cancer.
- It effectively induces antitumor immunity, characterized by specific immune responses and tumor necrosis, with a favorable safety profile compared to traditional therapies.
- The vaccine's slow, long-term release mechanism may enhance immune stimulation and cellular memory for sustained antitumor effects.
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