Interleukin-21: biology and application to cancer therapy

Abstract

Background: IL-21, a recently described common γ-chain cytokine, can induce the maturation and enhanced cytotoxicity of natural killer (NK) and CD8⁺ T cells and proliferation of CD40-stimulated B cells. Exogenous IL-21 has antitumor effects in murine models via immunological mechanisms. In addition, IL-21 can also directly induce apoptosis in chronic lymphocytic leukemia cells and other B cell lymphomas. Objective/methods: We examine preclinical and clinical data regarding anticancer therapy with IL-21. Published original research, abstracts and ongoing clinical trials are reviewed. A brief summary of IL-21 biology is also provided. Conclusion: Three Phase I and II clinical trials with recombinant IL-21 have been completed, providing data on the safety and efficacy in subjects with advanced melanoma, renal cell carcinoma and non-Hodgkin's B cell lymphoma. Numerous additional single-agent and combination therapy clinical trials are ongoing for a variety of human malignancies. B cell malignancies in particular warrant further clinical investigation.

Keywords::

• ADCC
• chronic lymphocytic leukemia
• cytokines
• cytotoxic T cells
• immunotherapy
• interleukin-21
• lymphoma
• melanoma
• NK cells
• renal cell carcinoma

Acknowledgements

JM Timmerman is the recipient of a Clinical Investigator Award from the Damon Runyon Cancer Research Foundation. DJ Andorsky is supported by grant T32 HL66992 from the National Institutes of Health, Bethesda, MD, USA.