Enhanced anti-colon cancer immune responses with modified eEF2-derived peptides

Weihong Sun, Xiaofang Wei, Airong Niu, Xuezhen Ma, Jian-Jian Li, Daiqing Gao

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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/Kb 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.

Original languageEnglish (US)
Pages (from-to)112-123
Number of pages12
JournalCancer Letters
Volume369
Issue number1
DOIs
StatePublished - Dec 1 2015

Keywords

  • Adoptive immunotherapy
  • Colon cancer
  • CTL
  • Enhanced immunoresponse
  • HLA-A2.1-restricted
  • Modified epitope

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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