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Functional capacity of Mcl-1-specific cytotoxic T-cells

Leukemia volume 20, pages 1457–1458 (2006)Cite this article

The clone was used to test the capacity of Mcl-1-specific T-cells to kill cancer cells. Subsequently, the HLA-A3-positive melanoma cell lines FM3, FM9 and the HLA-A3-negative melanoma cell line FM6 were used as target cells. The Mcl-195–103-specific T-cell clone effectively lysed the HLA-A3-positive cells (FM3, FM9), whereas no cytotoxicity was observed against the HLA-A3-negative cell line FM6 (Figure 1b). All cancer cell lines were examined for Mcl-1 expression by RT–PCR and all expressed Mcl-1 (data not shown). To further examine the antigen specificity and HLA restriction of the clone we examined inhibition of lysis of FM3 by the addition of the HLA-specific monoclonal antibody W6/32, and in cold target inhibition assays. The lysis of the melanoma cell line FM3 could be completely blocked by incubation of target cells with the antibody (Figure 1b). Likewise, the addition of cold (unlabeled) T2 cells pulsed with the Mcl-1 peptide blocked the lysis of FM3 tumor cells, whereas the addition of T2 cells without peptide only showed a limited dilution effect. These findings illustrate that cancer cells indeed process and present the Mcl-1 peptide in the context of the HLA-A3 molecule.

Moreover, we tested the ability of Mcl-1-specific CTLs to lyse human malignant cells enriched from a patient with acute myelogenous leukemia (AML). Consequently, we depleted T-cells and B-cells (CD3+, CD19+) from the bone marrow of an AML patient. The highly enriched AML cells were used as target cells in a standard 51Cr release assay. As shown in Figure 1c the Mcl-1-specific T-cell clone efficiently lysed the enriched leukemia cells in a HLA-dependent manner. Thus, inhibition with W6/32 or cold target cells (peptide pulsed T2-A3) completely abrogated killing. As an additional control, we used the HLA-A3-negative AML cell line HL-60 (kindly provided by Ove Juul Nielsen the State Hospital, Denmark) as control. The Mcl-1-specific T-cell clone did not kill this cell line (Figure 1c).

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Acknowledgements

We thank Inge Marie Svane, Herlev University Hospital for collection of blood samples. We thank Professor A. Svejgaard and Ms. Bodil K. Jakobsen, Department of Clinical Immunology, University Hospital, Copenhagen, for HLA-typing of patient blood samples. This study was supported by grants from the Danish Medical Research Council, The Novo Nordisk Foundation, The Danish Cancer Society, The John and Birthe Meyer Foundation, and Danish Cancer Research Foundation.

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  1. Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark

    R B Sørensen, P thor Straten & M H Andersen

  2. Department of Hematology, State University Hospital, Copenhagen, Denmark

    O J Nielsen

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  1. R B Sørensen
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  2. O J Nielsen
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  3. P thor Straten
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Sørensen, R., Nielsen, O., thor Straten, P. et al. Functional capacity of Mcl-1-specific cytotoxic T-cells. Leukemia 20, 1457–1458 (2006). https://doi.org/10.1038/sj.leu.2404261

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