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Chronic Myeloproliferative Disorders

A novel MHC-associated Proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias

Leukemia volume 20, pages 1067–1072 (2006)Cite this article

Abstract

Three of the most promising antigens for immunotherapy of chronic myelogenous leukaemia (CML) include the specific fusion-protein, Bcr/Abl, and the overexpressed proteins WT1 and Proteinase 3. The clinical significance of Proteinase 3 as a target in myelogenous leukaemias has been bolstered by detection of high frequencies of cytotoxic CD8+ lymphocytes specific for this antigen in patients undergoing immune therapies. Our investigation aimed to directly identify MHC-ligands derived from these antigens and presented on CML blasts by means of affinity-purification and mass spectrometric peptide-sequencing. Although no known or potential new epitopes were discovered for Bcr/Abl or WT1, a novel peptide from Proteinase 3 was detected among the more abundant MHC-ligands. Additionally, MHC-ligands derived from known immunogenic proteins overexpressed as a result of Bcr/Abl transformation were also identified. Our investigation is the second of only a small number of studies to identify a peptide from Proteinase 3 among the more abundant MHC-associated peptides and thus implies that peptides from this antigen are among the more abundantly presented of the known leukaemic antigens. Taken in conjunction with clinical observations of functional Proteinase 3 specific CTL in patients’, these data further support the application of this antigen as an immunotherapeutical target for myelogenous leukaemias.

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Acknowledgements

The authors would like to acknowledge Drs J Tolson and M Deeg for their assistance with the interpretation of peptide fragmentation spectra and HPLC-analysis. This work was partly supported by the European Commission; projects Outcome and Impact of Specific Treatment in European Research in Melanoma [OISTER], (contract: QLG1-CT-2002-00668) and European Network for the Identification and validation of antigens and biomarkers in cancer [ENACT], (contract: 6FP-CT-503306). We would like to thank Dr Ken Mills for the BCR-ABL transcript analysis.

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Author notes

  1. T Flad

    Present address: PANATecs GmbH, Ob dem Himmelreich 7, 72074, Tübingen, Germany

  2. L Mueller

    Present address: Glycotope GmbH, Robert-Rössle-Str. 10, 13125, Berlin, Germany

Authors and Affiliations

  1. Section for Transplantation Immunology and Immunohaematology, University Hospital Tübingen, ZMF, Waldhörnlestrasse 22, Tübingen, Germany

    A J Knights, T Flad, L Mueller & G Pawelec

  2. Department of Immunology, University Tübingen, Auf der Morgenstelle 15, Tübingen, Germany

    A O Weinzierl & S Stevanovic

  3. Department of Haematological Medicine, King's College London School of Medicine, The Rayne Institute, London, UK

    B-a Guinn & G J Mufti

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  1. A J Knights
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Correspondence to A J Knights.

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Knights, A., Weinzierl, A., Flad, T. et al. A novel MHC-associated Proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias. Leukemia 20, 1067–1072 (2006). https://doi.org/10.1038/sj.leu.2404234

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