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STEAP, a prostate tumor antigen, is a target of human CD8+ T cells

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Abstract

STEAP is a recently identified protein shown to be particularly overexpressed in prostate cancer and also present in numerous human cancer cell lines from prostate, pancreas, colon, breast, testicular, cervical, bladder and ovarian carcinoma, acute lymphocytic leukemia and Ewing sarcoma. This expression profile renders STEAP an appealing candidate for broad cancer immunotherapy. In order to investigate if STEAP is a tumor antigen that can be targeted by specific CD8+ T cells, we identified two high affinity HLA-A*0201 restricted peptides (STEAP86–94 and STEAP262–270). These peptides were immunogenic in vivo in HLA-A*0201 transgenic HHD mice. Peptide specific murine CD8 T cells recognized COS-7 cells co-transfected with HHD (HLA-A*0201) and STEAP cDNA constructs and also HLA-A*0201+ STEAP+ human tumor cells. Furthermore, STEAP86–94 and STEAP262–270 stimulated specific CD8+ T cells from HLA-A*0201+ healthy donors, and these peptide specific CD8+ T cells recognized STEAP positive human tumor cells in an HLA-A*0201-restricted manner. Importantly, STEAP86–94-specific T cells were detected and reactive in the peripheral blood mononuclear cells in NSCLC and prostate cancer patients ex vivo. These results show that STEAP can be a target of anti-tumor CD8+ T cells and that STEAP peptides can be used for a broad-spectrum-tumor immunotherapy.

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Acknowledgments

We thank Dr. Francine Jotereau (Inserm U463, Nantes, France) for providing tumor cell lines used in this study. This work was supported by grants from the INSERM (PROGRES), the Ligue Nationale contre le Cancer (Comité de Paris) and the Association pour la Recherche contre le Cancer (ARC #5129). PMSA is a fellow of the Fundação para a Ciência e a Tecnologia (PRAXIS XXI/BD/11252/97)—Portugal and ARC(ML/MLD/CM-A01/1). PMSA is a student of Oporto University’s GABBA (Programa Graduado em Biologia Básica e Aplicada) program, Portugal. OF is a fellow of the Association Nationale de la Recherche Technique (ANRT).

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Authors and Affiliations

  1. INSERM 487, Institut Gustave Roussy, 94805, Villejuif, France

    Pedro M. S. Alves, Olivier Faure, Stéphanie Graff-Dubois, Sebastien Cornet, David-Alexandre Gross, Isabelle Miconnet, Salem Chouaib & Kostas Kosmatopoulos

  2. Unité d’Immunité Cellulaire Antivirale, Institut Pasteur, 75015, Paris, France

    François A. Lemonnier

  3. ImmunoDesigned Molecules (IDM), 75011, Paris, France

    Olivier Faure

  4. Department of Medicine, Institut Gustave Roussy, 94805, Villejuif, France

    Karim Fizazi & Jean Charles Soria

  5. Blood Bank—University Hospital, 71110, Heraklion, Crete, Greece

    Irena Bolonakis

  6. Laboratoire d’Onco-immunologie Clinique, Ludwig Institute for Cancer Research, Hôpital Orthopédique, Niveau 5, Allée Est. Av. Pierre-Decker 4, 1005, Lausanne, Switzerland

    Pedro M. S. Alves

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  1. Pedro M. S. Alves
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  2. Olivier Faure
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  3. Stéphanie Graff-Dubois
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  4. Sebastien Cornet
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  5. Irena Bolonakis
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  6. David-Alexandre Gross
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  7. Isabelle Miconnet
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  8. Salem Chouaib
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  9. Karim Fizazi
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  10. Jean Charles Soria
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  11. François A. Lemonnier
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  12. Kostas Kosmatopoulos
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Correspondence to Pedro M. S. Alves.

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Alves, P.M.S., Faure, O., Graff-Dubois, S. et al. STEAP, a prostate tumor antigen, is a target of human CD8+ T cells. Cancer Immunol Immunother 55, 1515–1523 (2006). https://doi.org/10.1007/s00262-006-0165-3

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  • DOI: https://doi.org/10.1007/s00262-006-0165-3

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