Specific Targeting of a Naturally Presented Osteosarcoma Antigen, Papillomavirus Binding Factor Peptide, Using an Artificial Monoclonal Antibody
| Autor: | Hiroshi Matsumiya, Toshihiko Torigoe, Noriyuki Sato, Shingo Ichimiya, Vitaly Kochin, Masanori Kyono, Makoto Emori, Tadashi Hasegawa, Tetsuo Himi, Takahisa Hirano, Norihiro Muroi, Toshihiko Yamashita, Takuro Wada, Hiroko Asanuma, Shingo Toji, Keiji Yamashita, Kenji Murata, Kazue Watanabe, Tomohide Tsukahara |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.drug_class
Molecular Sequence Data Immunology Antigen presentation Bone Neoplasms Monoclonal antibody Cancer Vaccines Biochemistry Epitope Antigen Antigens Neoplasm Peptide Library Cell Line Tumor HLA-A2 Antigen medicine Humans Single-chain variable fragment Cytotoxic T cell Amino Acid Sequence Peptide library Papillomaviridae Molecular Biology Antigen Presentation Osteosarcoma Base Sequence Chemistry Antibodies Monoclonal Immunotherapy Active Cell Biology Virology HLA-B Antigens Cancer research Clone (B-cell biology) Single-Chain Antibodies T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Biological Chemistry. 289:22035-22047 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.568725 |
| Popis: | Osteosarcoma is a rare but highly malignant tumor occurring most frequently in adolescents. The prognosis of non-responders to chemotherapy is still poor, and new treatment modalities are needed. To develop peptide-based immunotherapy, we previously identified autologous cytotoxic T lymphocyte-defined osteosarcoma antigen papillomavirus binding factor (PBF) in the context of HLA-B55 and the cytotoxic T lymphocyte epitope (PBF A2.2) presented by HLA-A2. PBF and HLA class I are expressed in ∼90 and 70% of various sarcomas, respectively. However, the expression status of peptide PBF A2.2 presented by HLA-A2 on osteosarcoma cells has remained unknown because it is difficult to generate a specific probe that reacts with the HLA·peptide complex. For detection and qualification of the HLA-A*02:01·PBF A2.2 peptide complex on osteosarcoma cells, we tried to isolate a single chain variable fragment (scFv) antibody directed to the HLA-*A0201·PBF A2.2 complex using a naïve scFv phage display library. As a result, scFv clone D12 with high affinity (KD = 1.53 × 10(-9) M) was isolated. D12 could react with PBF A2.2 peptide-pulsed T2 cells and HLA-A2+PBF+ osteosarcoma cell lines and simultaneously demonstrated that the HLA·peptide complex was expressed on osteosarcoma cells. In conclusion, scFv clone D12 might be useful to select candidate patients for PBF A2.2 peptide-based immunotherapy and develop antibody-based immunotherapy. |
| Databáze: | OpenAIRE |
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