The identification of novel targets for
cancer immunotherapy and the development of new
vaccine immunogens are subjects of permanent interest. MUC1 is an overexpressed
antigen found in most
tumors, and its overexpression correlates with poor prognosis. Many attempts to direct the immune response against MUC1 in
tumor cells have failed, including several clinical trials. We have previously developed an innovative Variable
Epitope Library (VEL)
vaccine platform that carries massively substituted mutant variants of defined
epitopes or
epitope regions as an alternative to using wild-type
peptide sequences-based immunogens. Here, two murine MUC1-derived
epitopes equivalent to the previously tested in
cancer immunotherapy human MUC1 regions were used to generate VELs. We observed that vaccination with the 23L VEL immunogens, encompassing the entire
signal peptide region of MUC1, reduces the
tumor area compared to the wild-type sequence treatment. Contrastingly, vaccination with the MUC1
signal peptide-derived predicted CD8++ T cell
epitope-based VEL, 9MUC1spL, showed similar
tumor area reduction as the wild-type treatment; however, a decrease in lung
metastasis after 9MUC1spL treatment was observed. In addition, vaccination induced a large pool of CD8+ T cells which recognized most variant
epitopes from 9MUC1spL. Also, we generated MUC1 variable number tandem repeat (VNTR)-based VELs that reduced the metastatic burden when dendritic cells and M13 recombinant bacteriophages were used as
vaccine carriers. Collectively, our data demonstrate the immunogenic and antitumor properties of MUC1
signal peptide- and VNTR-derived VEL immunogens.