Enhanced anti-colon cancer immune responses with modified eEF2-derived peptides. Issue 1 (1st December 2015)

• Record Type: Journal Article
• Authors: Sun, Weihong; Wei, Xiaofang; Niu, Airong; Ma, Xuezhen; Li, Jian Jian; Gao, Daiqing
• Is Part Of: Cancer letters. Volume 369:Issue 1(2016)
• Page Start: 112
• Page End: 123
• Publication Date: 2015-12-01
• Subjects: eEF2 eukaryotic elongation factor-2 -- TAAs tumor-associated antigens -- PBLs peripheral blood lymphocytes -- Tg transgenic -- TCR T cell receptor -- GrB granzyme B -- CTL cytotoxic T lymphocyte -- PBMCs peripheral blood mononuclear cells -- DC dendritic cell -- DMSO dimethyl sulfoxide -- PBS phosphate-buffered saline -- mAb monoclonal antibody -- OVA ovalbumin -- FI fluorescence index -- MFI mean fluorescence intensities -- FITC fluorescein isothiocyanate -- CAP-1 carcinoembryonic antigen peptide-1 -- E:T effector:target; Adoptive immunotherapy -- Colon cancer -- CTL -- Enhanced immunoresponse -- Modified epitope -- HLA-A2.1-restricted; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.08.002
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: The peptide from eEF2, P739–747 (RLMEPIYLV), elicits CTL responses in vivo and in vitro . The modifications in P739–747 sequence improve the immunogenicity against eEF2. Analog peptides with HLA-A*0201 anchor induces CTLs with cross-reactive to the native peptide. The modified analogs inhibit tumor growth more efficiently than the native peptides. 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/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.