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Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor
Shuquan Zhang1, Yu Liu1, Ji Zhou1
1School of Pharmaceutical Sciences, Nation-Regional Engineering Lab for Synthetic Biology of Medicine, International Cancer Center, Shenzhen University Health Science Center, Shenzhen 518060, China.
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.
Insights
A novel MUC1 tumor vaccine, combining a Toll-like receptor 7 (TLR7) agonist and aluminum adjuvant, shows efficacy and safety. This MUC1 vaccine candidate demonstrates potential for breast cancer prevention and treatment by enhancing immune responses.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Mucin 1 (MUC1) is highly expressed in breast cancer, functioning as a cancer antigen.
- Small-molecule Toll-like receptor 7 (TLR7) agonists are investigated for tumor immunotherapy.
Purpose of the Study:
- To construct and evaluate a novel tumor vaccine (SZU251 + MUC1 + Al) for MUC1-expressing tumors.
- To assess the vaccine's immunostimulatory effects, efficacy, and safety in vitro and in vivo.
Main Methods:
- In vitro: assessed cytokine release and costimulatory molecule expression in mouse bone marrow dendritic cells (BMDCs) and spleen lymphocytes.
- In vivo: evaluated vaccine efficacy and safety in prophylactic and therapeutic models against MUC1-expressing tumors.
- Immune response analysis: measured antibody titers, CD4+, CD8+, and activated CD8+ T cell populations.
Main Results:
- The SZU251 + MUC1 + Al vaccine promoted cytokine release and costimulatory molecule expression in vitro.
- The vaccine demonstrated efficacy and safety in both prophylactic and therapeutic settings in vivo.
- Significant increases in specific humoral and cellular immunity, including antibody titers and T cell responses, were observed.
Conclusions:
- The novel MUC1 vaccine candidate (SZU251 + MUC1 + Al) effectively elicits anti-tumor immune responses.
- This vaccine shows promise for the prevention and treatment of breast cancer.
- Further investigation into its clinical application for breast cancer patients is warranted.
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