Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors
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Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors. / Andersen, Rikke Sick; Sørensen, Rikke Bæk; Ritter, Cathrin; Svane, Inge Marie; Becker, Jürgen C; thor Straten, Per; Andersen, Mads Hald.
In: Cancer Immunology, Immunotherapy, Vol. 60, No. 2, 2011, p. 227-34.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors
AU - Andersen, Rikke Sick
AU - Sørensen, Rikke Bæk
AU - Ritter, Cathrin
AU - Svane, Inge Marie
AU - Becker, Jürgen C
AU - thor Straten, Per
AU - Andersen, Mads Hald
PY - 2011
Y1 - 2011
N2 - With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells. Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-¿ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors.
AB - With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells. Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-¿ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors.
U2 - http://dx.doi.org/10.1007/s00262-010-0933-y
DO - http://dx.doi.org/10.1007/s00262-010-0933-y
M3 - Journal article
VL - 60
SP - 227
EP - 234
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
SN - 0340-7004
IS - 2
ER -
ID: 40197006