Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor Effects

含有新型 Toll 样受体 7 激动剂和铝佐剂的乳腺癌疫苗具有抗肿瘤作用

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Abstract

Mucin 1 (MUC1) has received increasing attention due to its high expression in breast cancer, in which MUC1 acts as a cancer antigen. Our group has been committed to the development of small-molecule TLR7 (Toll-like receptor 7) agonists, which have been widely investigated in the field of tumor immunotherapy. In the present study, we constructed a novel tumor vaccine (SZU251 + MUC1 + Al) containing MUC1 and two types of adjuvants: a TLR7 agonist (SZU251) and an aluminum adjuvant (Al). Immunostimulatory responses were first verified in vitro, where the vaccine promoted the release of cytokines and the expression of costimulatory molecules in mouse BMDCs (bone marrow dendritic cells) and spleen lymphocytes. Then, we demonstrated that SZU251 + MUC1 + Al was effective and safe against a tumor expressing the MUC1 antigen in both prophylactic and therapeutic schedules in vivo. The immune responses in vivo were attributed to the increase in specific humoral and cellular immunity, including antibody titers, CD4(+), CD8(+) and activated CD8(+) T cells. Therefore, our vaccine candidate may have beneficial effects in the prevention and treatment of breast cancer patients.

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