Combined IL-15/IL-15Rα Immunotherapy Maximizes IL-15 Activity In Vivo

Content Provider	Scilit
Author	Stoklasek, Thomas A. Schluns, Kimberly S. Lefrançois, Leo
Copyright Year	2006
Description	IL-15 has substantial potential as an immunotherapeutic agent for augmenting immune responses. However, the activity of IL-15 is mediated by a unique mechanism in which the cytokine is transpresented by cell-bound high-affinity IL-15Rα to target cells expressing the IL-15Rβ and the common γ-chain. Thus, the efficacy of administered IL-15 alone may be limited by the availability of free IL-15Rα. We now show that administration of soluble IL-15/IL-15Rα complexes greatly enhanced IL-15 half-life and bioavailability in vivo. Treatment of mice with this complex, but not with IL-15 alone, resulted in robust proliferation of memory CD8 T cells, NK cells, and NK T cells. The activity of the complex required IL-15Rβ, but not IL-15Rα, expression by the responding cells and was IL-7-independent. Interestingly, IL-15/IL-15Rα immunotherapy also caused naive CD8 T cell activation and development into effector cells and long-term memory T cells. Lastly, complexed IL-15, as compared with IL-15 alone, dramatically reduced tumor burden in a model of B16 melanoma. These findings hold significant importance for the use of IL-15 as a potential adjuvant/therapeutic and inducer of homeostatic proliferation, without the necessity for prior immunodepletion.
Ending Page	6080
Page Count	9
Starting Page	6072
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.177.9.6072
Journal	The Journal of Immunology
Issue Number	9
Volume Number	177
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2006-11-01
Access Restriction	Open
Subject Keyword	15/il 15rα Immunotherapy
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology