Eukaryotic elongation factor-2 (eEF2) is overexpressed in many human
cancers and is an attractive target for
cancer immunotherapy. The eEF2 derived
polypeptides have been shown to be able to induce cytotoxic T lymphocytes from healthy donor. Here, we demonstrate the evidence indicating that modification of a segment of
peptides from wild type eEF2-derived immunogenic
peptides is able to further enhance its capacity of inducing
antigen-specific cytotoxic T lymphocytes (CTLs) against
colon cancer cells. Using
peptide-MHC binding algorithms, potential HLA-A2.1-restricted
epitopes capable of inducing specific CD8(+) CTLs were identified. By analyzing HLA-A2.1 affinity and immunogenicity, we further identified one novel immunogenic
peptide, P739-747 (RLMEPIYLV), that elicited specific CTL responses in HLA-A2.1/K(b) transgenic mice and culture with peripheral blood lymphocytes from
colon cancer patients. Furthermore, replacing certain
amino acids (at positions 1, 3, 7) within the P739-747 sequence improved the immunogenicity against eEF2. Several analogs containing the auxiliary
HLA-A*0201 anchor residues were able to stably bind to
HLA-A*0201 and enhance CTL responses compared with the native sequence; two of them showed increased anti-
tumor effects during the adoptive immunotherapy in vivo. Thus, these results support that modified immunogenic analogs are promising candidates for
peptide-based
cancer vaccination and
immunotherapy.