Synthetic MUC1 breast cancer vaccine containing a Toll‑like receptor 7 agonist exerts antitumor effects

Liu,Yu; Tang,Li; Gao,Ningning; Diao,Yuwen; Zhong,Jingjing; Deng,Yongqiang; Wang,Zhulin; Jin,Guangyi; Wang,Xiaodong

doi:10.3892/ol.2020.11762

Synthetic MUC1 breast cancer vaccine containing a Toll‑like receptor 7 agonist exerts antitumor effects

Authors:
- Yu Liu
- Li Tang
- Ningning Gao
- Yuwen Diao
- Jingjing Zhong
- Yongqiang Deng
- Zhulin Wang
- Guangyi Jin
- Xiaodong Wang
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Affiliations: International Cancer Center, National‑Regional Engineering Lab for Synthetic Biology of Medicine, School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen, Guangdong 518055, P.R. China, Department of Oral and Maxillofacial Surgery, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen, Guangdong 518055, P.R. China
Published online on: June 19, 2020 https://doi.org/10.3892/ol.2020.11762
Pages: 2369-2377
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Adjuvant immunotherapy has recently emerged as a potential treatment strategy for breast cancer. The tumor‑associated protein mucin 1 (MUC1) has received increasing attention due to its high expression in numerous types of common tumors, in which MUC1 acts as a cancer antigen. However, the simple mixed composition of an adjuvant and a peptide is not a sufficient rationale for a MUC1 peptide‑based vaccine. The present study developed a novel Toll‑like receptor 7 (TLR7) agonist‑conjugated MUC1 peptide vaccine (T7‑MUC1), which elicited an effective immune response and a robust antitumor effect in a mouse breast cancer model. In vitro, T7‑MUC1 significantly increased the release of cytokines in mouse bone marrow dendritic cells and spleen lymphocytes, and induced the dendritic cell‑cytokine‑induced killer response against tumor cells with high MUC1 expression. In vivo, it was observed that the 4T1 tumor weights in mice immunized with the T7‑MUC1 conjugate were reduced by ≥70% compared with those in the control group. Furthermore, the therapeutic responses in vivo were attributed to the increase in specific humoral and cellular immunity, including high antibody titers, antibody‑dependent cell‑mediated cytotoxicity and cytotoxic T‑lymphocyte activity. The percentages of CD3+/CD8+ T‑cells were significantly higher in the T7‑MUC1 treatment group compared with those in the control group. Therefore, the results of the present study suggested that the T7‑MUC1 vaccine inhibited tumor growth in mice and thus may have potential as a therapeutic candidate in clinical trials for breast cancer immunotherapy.

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