Mucin 1 (MUC1) is a
tumor-associated
antigen that is overexpressed in several
adenocarcinomas. However, clinical trials with MUC1 showed that MUC1 is a relatively poor immunogen in humans. In view of the low immunogenicity of this
protein vaccine, we designed a method based on an
immunoadjuvant and immunization strategy to enhance the cellular immune response to this
protein vaccine.
DDA/MPL has been evaluated as an adjuvant to induce strong immunity for the
tuberculosis vaccine. However, its adjuvant role combined with the
vaccine targeting MUC1 in malignant
carcinomas has not previously been reported. Our previous study showed that adenovirus prime
protein boost vaccination could significantly enhance the cellular immunity and antitumor efficacy. In our study, we used MUC1 VNTRs as the target of
cancer vaccine and
DDA/MPL as the adjuvant to enhancing the cellular immunity of recombinant MUC1
protein vaccine, and an AD-9M adenoviral vector prime-
recombinant protein and
DDA/MPL boost (designated MUC-1 VPP
vaccine) strategy was studied to enhance the antitumor efficacy. The results demonstrated that
antigen-specific IFN-γ-secreting T cells were increased by 2-fold, and cytotoxic T lymphocytes (CTLs) were induced effectively when the
protein vaccine was combined with the
DDA/MPL adjuvant. Moreover, the vaccination induced nearly 60% inhibition of the growth of
B16 melanoma in mice and prolonged the survival of
tumor-bearing mice. The inhibition was correlated with the specific immune responses induced by the MUC1 VPP
vaccine. The data suggested that
DDA/MPL-adjuvant MUC-1 VPP
vaccine may be developed into effective
tumor vaccines for
melanomas and possibly for other
tumors expressing MUC1
protein.