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BCR/ABL-specific CD8+ T cells can be detected from CML patients, but are only expanded from healthy donors

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Abstract

The BCR/ABL p210 fusion protein has long been considered an ideal target antigen for the development of immunotherapeutic strategies in chronic myeloid leukaemia (CML) due to its central role in malignant transformation and to its unique novel amino acid sequence solely expressed in leukaemia cells. However, the feasibility to expand BCR-ABL-specific T cells remains still controversial. Using BCR/ABL peptide/MHC tetramers, significantly higher frequencies of tetramer positive cells were detected in the peripheral blood of HLA-A*0301 (mean 0.38%) and HLA-B*0801 (mean 0.28%) CML patients than in healthy donors (P = 0.0025 and 0.0026, respectively). However, following stimulation with autologous peptide-pulsed DCs, BCR/ABL-specific T cells were only expanded from some healthy donors, suggesting that CML patients may have a specific immune deficit with respect to the BCR/ABL antigen.

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Abbreviations

APC:

Antigen presenting cells

CML:

Chronic myelogenous leukaemia

CMV:

Cytomegalovirus

DC:

Dendritic cells

HLA:

Human leukocyte antigen

MHC:

Major histocompatibility complex

PBMC:

Peripheral blood mononuclear cells

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Acknowledgments

This work was supported by the Kay Kendall Leukaemia Fund and the European Union study No: 503319 “Allostem”.

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Authors and Affiliations

  1. The Anthony Nolan Research Institute, The Royal Free Hospital, University College of London, Medical School, Fleet Road, Hampstead, London, NW3 2QG, UK

    Sylvie Rusakiewicz, Alejandro Madrigal, Paul Travers & Anthony I. Dodi

Authors
  1. Sylvie Rusakiewicz
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  2. Alejandro Madrigal
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  3. Paul Travers
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  4. Anthony I. Dodi
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Corresponding author

Correspondence to Alejandro Madrigal.

Additional information

Professor A. I. Dodi passed away recently.

This paper is an original contribution from the meeting which took place 28–29 May 2008 in Nottingham, UK, celebrating the contribution of Prof. A. I. “Tony” Dodi (29 January 2008) to the EU project “Network for the identification and validation of antigens and biomarkers in cancer and their application in clinical tumour immunology (ENACT)”.

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Rusakiewicz, S., Madrigal, A., Travers, P. et al. BCR/ABL-specific CD8+ T cells can be detected from CML patients, but are only expanded from healthy donors. Cancer Immunol Immunother 58, 1449–1457 (2009). https://doi.org/10.1007/s00262-009-0703-x

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  • DOI: https://doi.org/10.1007/s00262-009-0703-x

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