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The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination

Nature Medicine volume 14, pages 676–680 (2008)Cite this article

Abstract

An ideal vaccination strategy against tumors relies on specific antigens that are required for tumor maintenance1. For lymphoma, vaccination with subject-specific immunoglobulin idiotypes has had the most promising results2,3. Here we show that DNA vaccination with plasmids encoding portions of the cytoplasmic domain of anaplastic lymphoma kinase (ALK), which has been translocated in different fusion proteins necessary for the growth of anaplastic large cell lymphoma (ALCL)4, protects mice from local and systemic lymphoma growth. The protection is potent and long lasting and elicits ALK-specific interferon-γ responses and CD8+ T cell–mediated cytotoxicity. A combination of chemotherapy and vaccination significantly enhanced the survival of mice challenged with ALK+ lymphomas. These findings indicate that ALK represents an ideal tumor antigen for vaccination-based therapies of ALCL and possibly other ALK+ human tumors4,5,6,7.

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Figure 1: ALK vaccination prevents the growth of ALK+ lymphoma cells.
Figure 2: Efficacy of ALK vaccination in preventing disseminated lymphoma growth and in lymphoma therapy.
Figure 3: Cytotoxic activity and IFN-γ production in ALK-vaccinated mice.
Figure 4: Protection generated by ALK vaccination requires CD8+ T cells and IFN-γ production but not B cells.

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Acknowledgements

We thank A. Manazza, A. Cimino, S. Lanzardo and I. Merighi for their technical help. μMT mice were provided by T. Blankenstein (Institute of Immunology, Charité Campus Benjamin Franklin, Berlin, Germany). BALB-Prf1−/− mice were a gift from the Peter MacCallum Cancer Institute. This work was supported by US National Institutes of Health grant R01-CA90773 to G.I. and Compagnia di San Paolo, Torino.

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Author notes

  1. Cinzia Martinengo and Cristina Mastini: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Experimental Research and Medical Studies, University of Torino, Via Santena 7, Torino, 10126, Italy

    Roberto Chiarle, Cinzia Martinengo, Cristina Mastini, Chiara Ambrogio & Giorgio Inghirami

  2. Department of Biomedical Sciences and Human Oncology, University of Torino, Via Santena 7, Torino, 10126, Italy

    Roberto Chiarle, Chiara Ambrogio & Giorgio Inghirami

  3. Department of Clinical and Biological Sciences, Molecular Biotechnology Center, University of Torino, Via Nizza 52, Torino, 10126, Italy

    Cristina Mastini & Guido Forni

  4. Department of Pathology and New York Cancer Center, New York University School of Medicine, 550 First Avenue, New York, 10016, USA

    Valentina D'Escamard & Giorgio Inghirami

Authors
  1. Roberto Chiarle
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  7. Giorgio Inghirami
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Contributions

R.C. contributed to the design, execution and analysis of the experiments and wrote the paper; C. Martinengo, C. Mastini, C.A. and V.D. contributed to the execution and analysis of the experiments; G.F. and G.I. contributed to the design of the experiments and to the writing of the paper.

Corresponding authors

Correspondence to Roberto Chiarle or Giorgio Inghirami.

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Chiarle, R., Martinengo, C., Mastini, C. et al. The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination. Nat Med 14, 676–680 (2008). https://doi.org/10.1038/nm1769

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