Osteosarcoma is the most common
malignancy of bone that affects young people.
Neoadjuvant chemotherapy and surgery have significantly improved the prognosis. However, the prognosis of non-responders to
chemotherapy is still poor. To develop
peptide-based
immunotherapy for
osteosarcoma, we previously identified CTL
epitopes derived from papillomavirus binding factor (PBF) in the context of
human leukocyte antigen (HLA)-A2,
HLA-A24 and
HLA-B55. In the present study, we identified two novel CTL
epitopes, QVT (QVTVWLLEQK) and LSA (LSALPPPLHK), in the context of
HLA-A11 using a sequence of screenings based on the predicted affinity of
peptides, in vitro folding ability of
peptide/
HLA-A11 complex, reactivity of
peptide/
HLA-A11 tetramer and
interferon (IFN)-γ production of T cells that was induced by mixed lymphocyte
peptide culture under a limiting dilution condition. CTL clones directed to QVT and LSA
peptides showed specific cytotoxicity against HLA-A11+ PBF+
osteosarcoma (HOS-A11) cells. In contrast, another
epitope, ASV (ASVLSRRLGK), could highly induce cognate tetramer-positive CTL. This might be because the ASV
peptide mimics the
peptide ASV (R6Q) (ASVLSQRLGK) derived from bacterial
polypeptides, ROK family
proteins. However, ASV-induced CTL did not show
cytokine production against the cognate
peptide. In conclusion, the CTL
epitopes QVT and LSA
peptides might be useful for the development of
immunotherapy targeting PBF for patients with
osteosarcoma.