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Idiotype-specific CD4+ T cells eradicate disseminated myeloma

Leukemia volume 30, pages 1216–1220 (2016)Cite this article

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T-cell immunotherapy is emerging as a very promising immunotherapeutic treatment strategy, and is the subject of numerous ongoing clinical trials in the management of various malignant diseases. Little is known about the therapeutic potential of adoptive T-cell therapy (ACT) in diseases affecting the bone marrow. The unique growth pattern of myeloma cells, with early dissemination and a predilection for the bone marrow compartment, raises important issues about the accessibility of such cells to T-cell immunotherapy. Similar patterns of tumor cell distribution are observed in other hematological malignancies, as well as in the advanced stages of other malignant diseases, where bone marrow metastases are a common occurrence. We therefore wanted to explore the applicability of T-cell therapy in the setting of multiple myeloma.

Whereas most studies of ACT have focused on direct recognition of tumor cells by cytotoxic CD8+ T cells, it is increasingly apparent that CD4+ T cells may also contribute to tumor rejection in mice and humans.1 We have previously demonstrated that mice harboring CD4+ T cells reactive against the monoclonal Ig V regions (idiotype; Id) secreted by the IgA+ MOPC315 plasmacytoma cell line are protected against tumor development upon subcutaneous challenge.2, 3 The Id-specific T cells recognize a mutated epitope localized within the variable region CDR3 loop of the λ2315 Ig light chain, presented on I-Ed MHC class II molecules.4 As the tumor cells do not themselves express detectable levels of MHC class II, T cell activation appears to be dependent on uptake and display of secreted antigen by tumor-infiltrating macrophages.5 Upon T cell engagement, the macrophages are rendered cytotoxic to surrounding tumor cells, leading to tumor rejection.2

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Acknowledgements

We thank Harald Carlsen for his contribution to the development of the MOPC315.BM model, Hilde Omholt and Melanie Manzke for technical assistance. This work was supported by grants from Helse Sør-Øst and the Norwegian Cancer Society.

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Author notes

  1. O A Haabeth and A Tveita: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway

    O A Haabeth, A Tveita, M Fauskanger, K Hennig & B Bogen

  2. Department of Immunology, KG Jebsen Centre for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital,

    P O Hofgaard & B Bogen

  3. Rikshospitalet, Oslo, Norway

    P O Hofgaard & B Bogen

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  1. O A Haabeth
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  2. A Tveita
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  5. P O Hofgaard
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  6. B Bogen
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Correspondence to O A Haabeth.

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Haabeth, O., Tveita, A., Fauskanger, M. et al. Idiotype-specific CD4+ T cells eradicate disseminated myeloma. Leukemia 30, 1216–1220 (2016). https://doi.org/10.1038/leu.2015.278

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