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HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor.


ABSTRACT:

Background

To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF) as a CTL-defined osteosarcoma antigen in the context of HLA-B55. However, clinical application of PBF-based immunotherapy requires identification of naturally presented CTL epitopes in osteosarcoma cells in the context of more common HLA molecules such as HLA-A2.

Methods

Ten peptides with the HLA-A*0201 binding motif were synthesized from the amino acid sequence of PBF according to the BIMAS score and screened with an HLA class I stabilization assay. The frequency of CTLs recognizing the selected PBF-derived peptide was determined in peripheral blood of five HLA-A*0201+ patients with osteosarcoma using limiting dilution (LD)/mixed lymphocyte peptide culture (MLPC) followed by tetramer-based frequency analysis. Attempts were made to establish PBF-specific CTL clones from the tetramer-positive CTL pool by a combination of limiting dilution and single-cell sorting. The cytotoxicity of CTLs was assessed by 51Cr release assay.

Results

Peptide PBF A2.2 showed the highest affinity to HLA-A*0201. CD8+ T cells reacting with the PBF A2.2 peptide were detected in three of five patients at frequencies from 2 x 10-7 to 5 x 10-6. A tetramer-positive PBF A2.2-specific CTL line, 5A9, specifically lysed allogeneic osteosarcoma cell lines that expressed both PBF and either HLA-A*0201 or HLA-A*0206, autologous tumor cells, and T2 pulsed with PBF A2.2. Five of 12 tetramer-positive CTL clones also lysed allogeneic osteosarcoma cell lines expressing both PBF and either HLA-A*0201 or HLA-A*0206 and T2 pulsed with PBF A2.2.

Conclusion

These findings indicate that PBF A2.2 serves as a CTL epitope on osteosarcoma cells in the context of HLA-A*0201, and potentially, HLA-A*0206. This extends the availability of PBF-derived therapeutic peptide vaccines for patients with osteosarcoma.

SUBMITTER: Tsukahara T 

PROVIDER: S-EPMC2702281 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor.

Tsukahara Tomohide T   Kawaguchi Satoshi S   Torigoe Toshihiko T   Takahashi Akari A   Murase Masaki M   Kano Masanobu M   Wada Takuro T   Kaya Mitsunori M   Nagoya Satoshi S   Yamashita Toshihiko T   Sato Noriyuki N  

Journal of translational medicine 20090612


<h4>Background</h4>To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF) as a CTL-defined osteosarcoma antigen in the context of HLA-B55. However, clinical application of PBF-based immunotherapy requires identification of naturally presented CTL epitopes in osteosarcoma cells in the context of more common HLA molecules such as HLA-A2.<h4>Methods</h4>Ten peptides with the HLA-A*0201 binding motif were synthesized from the amino acid  ...[more]

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