Three different vaccines based on the 140-amino acid MUC1 peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus MUC1-transgenic mice with different potential for tumor rejection

Low-frequency CTL and low-titer IgM responses against tumor-associated Ag M UC1 are present in cancer patients but do not prevent cancer growth. Boosti ng MUC1-specific immunity with vaccines, especially effector mechanisms res ponsible for tumor rejection, is an important goal. We studied immunogenici ty, tumor rejection potential, and safety of three vaccines: 1) MUC1 peptid e admixed with murine GM-CSF as an adjuvant; 2) MUC1 peptide admixed with a djuvant SB-AS2; and 3) MUC1 peptide-pulsed dendritic cells (DC). We examine d the qualitative and quantitative differences in Immoral and T cell-mediat ed MUC1-specific immunity elicited in human MUC1-transgenic (Tg) mice compa red with wild-type (WT) mice. Adjuvant-based vaccines induced MUC1-specific Abs but failed to stimulate MUC1-specific T cells. MUC1 peptide with GM-CS F induced IgG1 and IgG2b in WT mice but only IgM in MUC1-Tg mice. MUC1 pept ide with SB-AS2 induced high-titer IgG1, IgG2b, and IgG3 Abs in both WT and MUC1-Tg mice. Induction of IgG responses was T cell independent and did no t have any effect on tumor growth. MUC1 peptide-loaded DC induced only T ce ll immunity. If injected together with soluble peptide, the DC vaccine also triggered Ab production. Importantly, the DC vaccine elicited tumor reject ion responses in both WT and MUC1-Tg mice. These responses correlated with the induction of MUC1-specific CD4(+) and CD8(+) T cells in WT mice, but on ly CD8(+) T cells in MUC1-Tg mice. Even though MUC1-specific CD4(+) T cell tolerance was not broken, the capacity of MUC1-Tg mice to reject tumor was not compromised.