Induction of Bcl-xL-Specific Cytotoxic T Lymphocytes in Mice

Authors

  • H. L. Larsen,

    1. Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • M. H. Andersen,

    1. Department of Hematology, Center for Cancer Immune Therapy (CCIT), Herlev University Hospital, Herlev, Denmark
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  • H. H. Wandall,

    1. Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • C. B. Madsen,

    1. Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    2. Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • R. E. Christensen,

    1. Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • T. R. Petersen,

    1. Malaghan Institute of Medical Research, Victoria University, Wellington, New Zealand
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  • A. E. Pedersen

    Corresponding author
    1. Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    • Correspondence to: A. E. Pedersen, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. E-mail: elmpedersen@sund.ku.dk

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Abstract

The induction of active immunity against tumour-associated antigens to prevent relapse of cancer is a promising approach but has so far shown only low efficacy. This low efficacy may in part be due to clonal escape of tumour cell variants by the downregulation of antigen expression or inflammation-induced dedifferentiation. Identification of novel tumour-associated antigens that at the same time are essential for continued tumour cell survival is thus critical for the development of active cancer vaccinations. At the same time, identification of novel endogenous murine tumour antigens will help improve preclinical development of cancer immunotherapy. The anti-apoptotic protein Bcl-xL has been suggested to be such an essential tumour antigen, but the lack of well-defined murine epitopes have delayed preclinical studies of Bcl-xL-targeting cancer vaccines. Here, we report the identification of two novel murine tumour-associated epitopes TAYQSFEQV and AFFSFGGAL derived from mouse Bcl-xL. Dendritic cell (DC)-based vaccination induced CD8+ T cells capable of producing IFN-γ upon restimulation with these epitopes. Thus, our data may benefit the design of future immunotherapy strategies by providing a preclinical model for cancer vaccination with an endogenous tumour antigen that can be combined with other cancer treatments.

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