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Preclinical validation of interleukin 6 as a therapeutic target in multiple myeloma

  • IMMUNOLOGY AT THE UNIVERSITY OF IOWA
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Abstract

Studies on the biologic and molecular genetic underpinnings of multiple myeloma (MM) have identified the pleiotropic, pro-inflammatory cytokine, interleukin-6 (IL-6), as a factor crucial to the growth, proliferation and survival of myeloma cells. IL-6 is also a potent stimulator of osteoclastogenesis and a sculptor of the tumor microenvironment in the bone marrow of patients with myeloma. This knowledge has engendered considerable interest in targeting IL-6 for therapeutic purposes, using a variety of antibody- and small-molecule-based therapies. However, despite the early recognition of the importance of IL-6 for myeloma and the steady progress in our knowledge of IL-6 in normal and malignant development of plasma cells, additional efforts will be required to translate the promise of IL-6 as a target for new myeloma therapies into significant clinical benefits for patients with myeloma. This review summarizes published research on the role of IL-6 in myeloma development and describes ongoing efforts by the University of Iowa Myeloma Multidisciplinary Oncology Group to develop new approaches to the design and testing of IL-6-targeted therapies and preventions of MM.

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Acknowledgments

This research was performed by TRR in partial fulfillment of the requirements for the degree Doctor of Philosophy in the Graduate Immunology Program of the University of Iowa. He wishes to thank Dr. Kristin Ness for expert technical assistance and mouse husbandry. This work was supported in part by NIH Predoctoral Training Grant 5T32 AI007485 (to TRR), by R01CA152105 from the NCI (to FZ); by a Translational Research Program award from the Leukemia and Lymphoma Society (to FZ); by institutional start-up funds from the Department of Internal Medicine, Carver School of Medicine, University of Iowa (to FZ and GT); by P30CA086862 from the NCI; by a Senior Research Award from the Multiple Myeloma Research Foundation (to SJ); by a career development award from NCI P50CA097274 (to SJ); and by R01CA151354 from the NCI (to SJ).

Conflict of interest

The authors declare no competing financial interest.

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Authors and Affiliations

  1. Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Timothy R. Rosean & Siegfried Janz

  2. Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Van S. Tompkins, Carol J. Holman, Alicia K. Olivier & Siegfried Janz

  3. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Guido Tricot & Fenghuang Zhan

  4. Myeloma Multidisciplinary Oncology Group, Holden Comprehensive Cancer Center, University of Iowa, 500 Newton Road, 1030 Medical Laboratories, Iowa City, IA, 52242, USA

    Guido Tricot, Carol J. Holman, Fenghuang Zhan & Siegfried Janz

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  1. Timothy R. Rosean
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  7. Siegfried Janz
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Correspondence to Siegfried Janz.

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Rosean, T.R., Tompkins, V.S., Tricot, G. et al. Preclinical validation of interleukin 6 as a therapeutic target in multiple myeloma. Immunol Res 59, 188–202 (2014). https://doi.org/10.1007/s12026-014-8528-x

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