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 language | English (US) |
|---|---|
| Pages (from-to) | 112-123 |
| Number of pages | 12 |
| Journal | Cancer Letters |
| Volume | 369 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2015 |
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Keywords
- Adoptive immunotherapy
- Colon cancer
- CTL
- Enhanced immunoresponse
- HLA-A2.1-restricted
- Modified epitope
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Medicine(all)
Cite this
Enhanced anti-colon cancer immune responses with modified eEF2-derived peptides. / Sun, Weihong; Wei, Xiaofang; Niu, Airong; Ma, Xuezhen; Li, Jian-Jian; Gao, Daiqing.
In: Cancer Letters, Vol. 369, No. 1, 01.12.2015, p. 112-123.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced anti-colon cancer immune responses with modified eEF2-derived peptides
AU - Sun, Weihong
AU - Wei, Xiaofang
AU - Niu, Airong
AU - Ma, Xuezhen
AU - Li, Jian-Jian
AU - Gao, Daiqing
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Adoptive immunotherapy
KW - Colon cancer
KW - CTL
KW - Enhanced immunoresponse
KW - HLA-A2.1-restricted
KW - Modified epitope
UR - http://www.scopus.com/inward/record.url?scp=84943456027&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943456027&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2015.08.002
DO - 10.1016/j.canlet.2015.08.002
M3 - Article
VL - 369
SP - 112
EP - 123
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -