Induction of immune response and anti-tumor activities in mice with a DNA vaccine encoding human mucin 1 variable-number tandem repeats

Abstract

Mucin 1 (MUC1) is a tumor-associated antigen that carries the important variable-number tandem repeat (VNTR) epitopes for inducing cytotoxic T lymphocytes. Such a property makes MUC1 VNTR potentially attractive for immunotherapy. This study explored the possibility of developing an efficient anti-tumor vaccine strategy using the specific antitumor immunity induced by the MUC1 VNTR DNA vaccine combined with the adjuvant effect of a plasmid expressing murine interleukin-2 (IL-2). The results showed that the MUC1 VNTR DNA vaccine successfully induced both humoral and cellular immune responses against MUC1 VNTR in mice. The effect could be obviously enhanced by increasing the number of tandem repeats, the number of immunizations, and by co-administration of the cytokine plasmid. The growth of MUC1-expressing (MUC1(+)) tumors was significantly inhibited in mice immunized with the MUC1 VNTR DNA vaccine combined with the IL-2 plasmid, both before and after tumor challenge. A much larger percentage of the immunized mice survived tumor challenge than the non-immunized mice. The combination of the MUC1 VNTR DNA vaccine and the IL-2 adjuvant plasmid provides an attractive alternative for prophylactic and therapeutic vaccinations against MUC1(+) tumors.