IMMUNOLOGY AT THE UNIVERSITY OF IOWA

Immunologic Research

, Volume 59, Issue 1, pp 188-202

First online:

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

  • Timothy R. RoseanAffiliated withInterdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa
  • , Van S. TompkinsAffiliated withDepartment of Pathology, Carver College of Medicine, University of Iowa
  • , Guido TricotAffiliated withDepartment of Internal Medicine, Carver College of Medicine, University of IowaMyeloma Multidisciplinary Oncology Group, Holden Comprehensive Cancer Center, University of Iowa
  • , Carol J. HolmanAffiliated withDepartment of Pathology, Carver College of Medicine, University of IowaMyeloma Multidisciplinary Oncology Group, Holden Comprehensive Cancer Center, University of Iowa
  • , Alicia K. OlivierAffiliated withDepartment of Pathology, Carver College of Medicine, University of Iowa
  • , Fenghuang ZhanAffiliated withDepartment of Internal Medicine, Carver College of Medicine, University of IowaMyeloma Multidisciplinary Oncology Group, Holden Comprehensive Cancer Center, University of Iowa
  • , Siegfried JanzAffiliated withInterdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of IowaDepartment of Pathology, Carver College of Medicine, University of IowaMyeloma Multidisciplinary Oncology Group, Holden Comprehensive Cancer Center, University of Iowa Email author 

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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.

Keywords

IL-6 signaling in neoplastic plasma cells Myeloma stem cells and minimal residual disease Small-drug- and monoclonal antibody-based inhibitors Genetically engineered mouse models of human myeloma