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Chromosomal aberrations in leukaemia cells may delete tumour target antigens of stem cell-based immunotherapy

Leukemia volume 20, pages 1298–1300 (2006)Cite this article

A novel approach to eliminate residual disease after human leucocyte antigen (HLA)-matched stem cell transplantation (SCT) for leukaemia is tumour-specific adoptive immunotherapy. Excellent immunotherapeutic targets for adoptive immunotherapy are the haematopoietic system-specific minor-histocompatibility antigens (mHags) HA-1 and HA-2, which are expressed on all normal and malignant haematopoietic cells.1, 2 HA-1 and HA-2 epitopes are presented on the cell surface in the binding groove of HLA-A2 molecules. Immunotherapy with HA-1 or HA-2-specific cytotoxic T lymphocytes (CTLs) is restricted to leukaemia patients positive for the immunogenic mHag HA-1 or HA-2 alleles, that is HA-1H or HA-2V, respectively. The mHag status of patients is routinely determined by allele-specific genomic polymerase chain reaction (PCR) on peripheral blood mononuclear cells (PBMCs).2 Generally, leukaemic cells have the same mHag allelic patterns as the PBMCs. Most leukaemias, however, have karyotypic abnormalities,3 some of which affect mHag encoding genomic regions (e.g. 19p13.3 harbouring the HA-1 gene4 or 7p12-13 harbouring the HA-2 gene5).

Here, we have shown as proof of principle that common karyotypic abnormalities in leukaemia cells can knockout mHag encoding genes and thereby abrogate their recognition by mHag CTLs. This antigen presentation defect is restricted to a very limited number of antigens, namely those affected by the chromosomal aberration. It differs thereby from previously described immune escape mechanisms like loss/downregulation of HLA expression6 or peptide processing defects,7 which broadly abolish antigen recognition on malignant cells. Consequently, the observed mechanism of mHag loss requires particular attention when targeting specific mHags with immunotherapy.

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Acknowledgements

This work was in part supported by the Dutch Cancer Society and the Deutsche Forschungsgemeinschaft. We thank Eric Spierings for fruitful discussions.

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Authors and Affiliations

  1. Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

    L Hambach, J J M Drabbels & Els Goulmy

  2. Department of Haematology, Leiden University Medical Center, Leiden, The Netherlands

    B A Nijmeijer & J H F Falkenburg

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  1. L Hambach
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  2. B A Nijmeijer
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  3. J J M Drabbels
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  4. J H F Falkenburg
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  5. Els Goulmy
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Correspondence to L Hambach.

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Hambach, L., Nijmeijer, B., Drabbels, J. et al. Chromosomal aberrations in leukaemia cells may delete tumour target antigens of stem cell-based immunotherapy. Leukemia 20, 1298–1300 (2006). https://doi.org/10.1038/sj.leu.2404237

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