Although peptide vaccines offer a novel venue for cancer immunotherapy, clinical success has been rather limited. Cell‑penetrating peptides, due to their ability to translocate through the cell membrane, could be conjugated to the peptide vaccine to enhance therapeutic efficiency. The S4 transduction domain of the shaker‑potassium channel was conjugated to mammaglobin‑A (MamA) immunodominant epitope (MamA2.1) to verify its anticancer immunogenicity. S4‑MamA2.1 peptide has demonstrated significantly higher epitope loading and stable membrane expression of HLA‑A2 antigen‑presenting molecules on T2 cell lines. Further, these S4‑MamA2.1 treated T2 cells were able to activate naïve CD8+ T cells to induce MamA‑specific cytotoxicity against breast cancer cells. Conjugation of the S4 domain has also demonstrated a slight increase in immunogenicity of lesser immunodominant MamA epitopes. The conjugation of the S4 domain to N‑terminus of MamA2.1 demonstrated significantly higher immunogenicity over C‑terminus conjugation. Taken together, the results of the present study suggest that conjugation of the S4 cell‑penetrating peptide domain to MamA2.1 epitope enhances the peptide vaccine immunogenicity against MamA‑expressing breast cancers.

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