Jun Guo, Guo Li and Jun Tang contributed equally to this work.
HLA-A2-restricted Cytotoxic T Lymphocyte Epitopes from Human Hepsin as Novel Targets for Prostate Cancer Immunotherapy
Article first published online: 22 AUG 2013
© 2013 John Wiley & Sons Ltd
Scandinavian Journal of Immunology
Volume 78, Issue 3, pages 248–257, September 2013
How to Cite
Guo, J., Li, G., Tang, J., Cao, X.-B., Zhou, Q.-Y., Fan, Z.-J., Zhu, B. and Pan, X.-H. (2013), HLA-A2-restricted Cytotoxic T Lymphocyte Epitopes from Human Hepsin as Novel Targets for Prostate Cancer Immunotherapy. Scandinavian Journal of Immunology, 78: 248–257. doi: 10.1111/sji.12083
- Issue published online: 22 AUG 2013
- Article first published online: 22 AUG 2013
- Accepted manuscript online: 31 MAY 2013 12:46AM EST
- Manuscript Accepted: 27 MAY 2013
- Manuscript Received: 30 NOV 2012
- National Nature Science Foundation of China. Grant Number: 30800520
- Nature Science Foundation of Nanjing Military Command. Grant Number: 11MA041
Hepsin is a type II transmembrane serine protease that is overexpressed in prostate cancer, and it is associated with prostate cancer cellular migration and invasion. Therefore, HPN is a biomarker for prostate cancer. CD8+ T cells play an important role in tumour immunity. This study predicted and identified HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitopes in human hepsin protein. HLA-A2-restricted CTL epitopes were identified using the following four-step procedure: (1) a computer program generated predicted epitopes from the amino acid sequence of human hepsin; (2) an HLA-A2-binding assay detected the affinity of the predicted epitopes to the HLA-A2 molecule; (3) the primary T cell response against the predicted epitopes was stimulated in vitro; and (4) the induced CTLs towards different types of hepsin- or HLA-A2-expressing prostate cancer cells were detected. Five candidate peptides were identified. The effectors that were induced by human hepsin epitopes containing residues 229 to 237 (Hpn229; GLQLGVQAV), 268 to 276 (Hpn268; PLTEYIQPV) and 191 to 199 (Hpn199; SLLSGDWVL) effectively lysed LNCaP prostate cancer cells that were hepsin-positive and HLA-A2 matched. These peptide-specific CTLs did not lyse normal liver cells with low hepsin levels. Hpn229, Hpn268 and Hpn199 increased the frequency of IFN-γ-producing T cells compared with the negative peptide. These results suggest that the Hpn229, Hpn268 and Hpn199 epitopes are novel HLA-A2-restricted CTL epitopes that are capable of inducing hepsin-specific CTLs in vitro. Hpn229, Hpn268 and Hpn199 peptide-based vaccines may be useful for immunotherapy in patients with prostate cancer.