Pre-clinical toxicity and immunogenicity evaluation of a MUC1–MBP/BCG anti-tumor vaccine

• MUC1–MBP/BCG anti-tumor vaccine is an immunotherapy that targets MUC1+ tumors.
• MUC1–MBP/BCG anti-tumor vaccine causes no obvious toxicity.
• MUC1–MBP/BCG anti-tumor vaccine induces a MUC1-specific Th1 immune response.
• MUC1–MBP/BCG anti-tumor vaccine induces a MUC1-specific IgG antibody response.

Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1–MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1–MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1–MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1–MBP/BCG anti-tumor vaccine into a Phase I clinical trial.