Antitumor effect of adenoviral vector prime protein boost immunity targeting the MUC1 VNTRs

Abstract

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.