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  • Original Article
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Immunology

Characterization of BAX inhibitor-1 as a novel leukemia-associated antigen

Leukemia volume 23, pages 1818–1824 (2009)Cite this article

Abstract

Using dendritic cells (DCs) electroporated with whole RNA isolated from blasts of a patient with acute myeloid leukemia (AML), we were able to generate leukemia-specific cytotoxic T lymphocytes (CTLs) capable of recognizing the leucemic cells. To identify T-cell epitopes mediating lysis of malignant cells, peptides were eluted from the patient's blasts and analyzed by mass spectrometry (LC/MS)-based peptide sequencing. Using this approach, an HLA-A24-binding peptide derived from Bax inhibitor-1 (BI-1), a regulator of apoptosis pathways, was identified as an epitope recognized by the generated CTLs. To further characterize this novel antigenic peptide, CTLs were induced using DCs electroporated with RNA coding for BI-1 or pulsed with the cognate peptide. These CTLs generated from healthy donors in vitro efficiently lysed the patient's blasts as well as other HLA-matched leukemic cells. In conclusion, we identified a BI-1 peptide as a novel immunogenic tumor-associated antigen (TAA) in AML. In vitro induction of BI-1-specific CTLs by RNA transfection or pulsing of DCs with the synthetically generated peptide was a feasible and highly effective method to generate leukemia-specific CTLs. As BI-1 is (over-) expressed in a broad variety of malignancies, it may represent an interesting novel TAA in the context of cancer vaccines.

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Acknowledgements

This study was supported by SFB 685. We thank Sylvia Stephan for excellent technical assistance.

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Author notes

  1. S M Schmidt and T König: These two authors contributed equally to this work.

  2. F Grünebach and P Brossart: These two authors share equal senior authorship.

Authors and Affiliations

  1. Department of Hematology, Oncology, Rheumatology and Immunology,

    S M Schmidt, T König & F Grünebach

  2. University of Tübingen, Tübingen, Germany

    S M Schmidt, T König & F Grünebach

  3. Department of Hematology and Oncology, University of Bonn, Bonn, Germany

    A Bringmann, S Held, K von Schwarzenberg, A Heine, T A W Holderried & P Brossart

  4. Department for Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany

    S Stevanovic

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  1. S M Schmidt
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Correspondence to P Brossart.

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Schmidt, S., König, T., Bringmann, A. et al. Characterization of BAX inhibitor-1 as a novel leukemia-associated antigen. Leukemia 23, 1818–1824 (2009). https://doi.org/10.1038/leu.2009.138

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