The Effect of Different Immunization Cycles of a Recombinant Mucin1-Maltose-Binding Protein Vaccine on T Cell Responses to B16-MUC1 Melanoma in Mice

Abstract

We explored the effect of a recombinant mucin1-maltose-binding protein vaccine, including immunization cycles of recombinant mucin1-maltose-binding protein (MUC1-MBP) and CpG 2006 on T cell responses to human MUC1-overexpressing mouse melanoma B16 cells (B16-MUC1) melanoma in mice. We found that the vaccine had a significant antitumor effect, with the most obvious tumor-suppressive effect being observed in mice immunized five times. After more than five immunizations, the tumor inhibition rate decreased from 81.67% (five immunizations) to 43.67% (eight immunizations). To study the possible mechanism, Mucin-1(MUC1)-specific antibodies, IFN-γ secretion by lymphocytes, and cytotoxic T lymphocyte (CTL) cytotoxicity were measured by enzyme-linked immunosorbent assay (ELISA) and a real-time cell analyzer (RTCA). T cell subsets and immunosuppressive cells in the mouse spleen and tumor microenvironment were analyzed by FACS. These results showed that five immunizations activated MUC1-specific Th1 and CTL and reduced the ratio of myeloid-derived suppressor cells (MDSCs) and Th17 in mice more significantly than eight immunizations, indicating that excessive frequency of the immune cycle leads to the increased numbers of immunosuppressive cells and decreased numbers of immunostimulatory cells, thereby inhibiting antitumor immune activity. This data provide an experimental foundation for the clinical application of a recombinant MUC1-MBP vaccine.

Mucin1 relieves acute lung injury by inhibiting inflammation and oxidative stress

“…Mice in the ALI and ALI+MUC1 groups were constructed in the ALI/ARDS model and mice in the ALI+MUC1 group were injected subcutaneously daily with recombinant mouse MUC1 protein (100 μg/kg) (Baize, Shanghai, China) daily one week prior to modeling. 10 The mouse ALI/ARDS modeling method is as follows: After anesthetizing the mice with sodium pentobarbital (50 mg/kg), we used tape to secure the mice in the supine position on the operating table. After wiping the neck skin of the mouse with an alcohol cotton ball, we use scissors to gently cut the neck skin and bluntly separate the neck muscles from both sides.…”

Dual roles of myeloid‑derived suppressor cells induced by Toll‑like receptor signaling in cancer (Review)

“…However, another study has reported that CpG indirectly upregulates the expression levels of CD11c, MHCII, CD80 and F4/80 on MDSCs through type I IFN produced by pDCs mediated by CpG ( 17 ), which may be attributed to CpG administration. Preclinical trials in our laboratory indicated that the recombinant mucin1-maltose-binding protein vaccine, including recombinant mucin1-maltose-binding protein and CpG 2006, significantly downregulated the ratio of MDSCs in the spleen and tumor microenvironment ( 94 ). Taken together, these studies provide a rationality for the application of CpG as a cancer vaccine adjuvant.…”