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Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses

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Abstract

Cytotoxic T lymphocytes (CTL) can kill Hodgkin’s lymphoma (HL) cells, and CTL have been used for the treatment of Epstein-Barr virus (EBV)-positive HL. For patients with EBV-negative HL, this strategy cannot be employed and alternative target structures have to be defined. In order to establish a system for the stimulation of HL-reactive T cells, we used dendritic cells (DC) as antigen-presenting cells for autologous T cells and transfected these DC with RNA from established HL cell lines. After stimulation of peripheral blood mononuclear cells (PBMC) with RNA-transfected DC, we analyzed the reactivity of primed PBMC by interferon gamma enzyme-linked immunospot. Our results suggest the presence of antigens with expression in HL cell lines and recognition of these antigens in combination with DC-derived human leukocyte antigen molecules. By the analysis of Gene Expression Omnibus microarray data sets from HL cell lines and primary HL samples in comparison with testis and other normal tissues, we identified HL-associated cancer testis antigens (CTA) including the preferentially expressed antigen in melanoma (PRAME). After stimulation of PBMC with RNA-transfected DC, we detected PRAME-reactive T cells. PRAME and other HL-associated CTA might be targets for HL-specific immune therapy or for the monitoring of HL-directed immune responses.

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Acknowledgments

This work was supported by grants from Peter-Escher-Foundation for children with cancer.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle, Germany

    Carolin Winkler, Daniela Max, Stefanie Kewitz, Ursula Banning-Eichenseer & Martin Sebastian Staege

  2. Institute of Quantum Optics, Leibniz University Hanover, 30167, Hanover, Germany

    Daniel Sebastian Steingrube

  3. HLA-Laboratory, Martin-Luther-University Halle-Wittenberg, 06120, Halle, Germany

    Wolfgang Altermann & Gerald Schlaf

  4. Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120, Halle, Germany

    Alexander Emmer & Malte Kornhuber

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  1. Carolin Winkler
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  2. Daniel Sebastian Steingrube
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Correspondence to Martin Sebastian Staege.

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Winkler, C., Steingrube, D.S., Altermann, W. et al. Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses. Cancer Immunol Immunother 61, 1769–1779 (2012). https://doi.org/10.1007/s00262-012-1239-z

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