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

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. Access through your institution Buy or subscribe This is a preview of

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LEADER SEQUENCE CATHEPSIN G-DERIVED PEPTIDE Article Open access 12 February 2025 SINGLE-CELL DERIVED TUMOR ORGANOIDS DISPLAY DIVERSITY IN HLA CLASS I PEPTIDE PRESENTATION Article Open access

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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. AUTHOR INFORMATION Author notes * T Flad Present address:

PANATecs GmbH, Ob dem Himmelreich 7, 72074, Tübingen, Germany * L Mueller Present address: Glycotope GmbH, Robert-Rössle-Str. 10, 13125, Berlin, Germany AUTHORS AND AFFILIATIONS * Section

for Transplantation Immunology and Immunohaematology, University Hospital Tübingen, ZMF, Waldhörnlestrasse 22, Tübingen, Germany A J Knights, T Flad, L Mueller & G Pawelec * Department

of Immunology, University Tübingen, Auf der Morgenstelle 15, Tübingen, Germany A O Weinzierl & S Stevanovic * Department of Haematological Medicine, King's College London School of

Medicine, The Rayne Institute, London, UK B-a Guinn & G J Mufti Authors * A J Knights View author publications You can also search for this author inPubMed Google Scholar * A O Weinzierl

View author publications You can also search for this author inPubMed Google Scholar * T Flad View author publications You can also search for this author inPubMed Google Scholar * B-a

Guinn View author publications You can also search for this author inPubMed Google Scholar * L Mueller View author publications You can also search for this author inPubMed Google Scholar *

G J Mufti View author publications You can also search for this author inPubMed Google Scholar * S Stevanovic View author publications You can also search for this author inPubMed Google

Scholar * G Pawelec View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to A J Knights. RIGHTS AND PERMISSIONS Reprints

and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download

citation * Received: 06 December 2005 * Revised: 09 March 2006 * Accepted: 14 March 2006 * Published: 20 April 2006 * Issue Date: 01 June 2006 * DOI: https://doi.org/10.1038/sj.leu.2404234

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clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * chronic myelogenous leukaemia * proteinase 3 * peptide sequencing & MHC-ligands