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

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.

Glycolipid‐peptide conjugate vaccines elicit CD8+ T‐cell responses and prevent breast cancer metastasis

“…Although we report robust protection against lung tumor colonies, we did not observe complete rejection of subcutaneously‐ or intramammary‐implanted tumors. This may be due to the immunosuppressive tumor stroma at primary tumor sites and is consistent with reports that cancer vaccine monotherapy fails to eliminate established tumors in other breast cancer models 48–50 . While it is possible that additional strategies, such as combining the vaccines with checkpoint blockade therapies or cytotoxic agents, might have improved control of the primary tumor, cancer vaccines are more likely to be used as adjuvant therapies to prevent metastasis, a role which our findings support.…”

Comparison of mucin-1 in human breast cancer and canine mammary gland tumor: a review study

“…MUC-1 and toll-like receptor 7 (TLR-7) peptide in a murine model of BC were tested, and this vaccine induced CTL response and antibody-dependent cellular cytotoxicity (ADCC) and improved humoral immunity against MUC-1 + cancer cells [ 61 ]. This vaccine might inhibit tumor growth and recurrence and showed significant cytotoxicity in vivo [ 61 ].…”

“…MUC-1 and toll-like receptor 7 (TLR-7) peptide in a murine model of BC were tested, and this vaccine induced CTL response and antibody-dependent cellular cytotoxicity (ADCC) and improved humoral immunity against MUC-1 + cancer cells [ 61 ]. This vaccine might inhibit tumor growth and recurrence and showed significant cytotoxicity in vivo [ 61 ]. A virus-like particle containing MUC-1 and survivin peptide was evaluated in a triple-negative breast cancer (TNBC) mice model, which specifically induced cytotoxicity and CTL response [ 62 ].…”

Advances in MUC1-Mediated Breast Cancer Immunotherapy

“…In this regard, there are several studies worthy of attention. Liu et al [ 146 ] synthesized a new MUC1 peptide vaccine conjugated with the toll-like receptor 7 (TLR7) agonist (denoted as T7-MUC1), which induced potent immunity and anticancer activity in a mouse model of BRCA. Moreover, T7-MUC1 remarkably promoted cytokine production in vitro within mouse splenic lymphocytes and bone marrow-derived DCs, while inducing a DC-cytokine-mediated anticancer killer response in MUC1-overexpressing cells.…”