| First Author | Stoklasek TA | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 9 | Pages | 6072-80 |
| PubMed ID | 17056533 | Mgi Jnum | J:140524 |
| Mgi Id | MGI:3814025 | Doi | 10.4049/jimmunol.177.9.6072 |
| Citation | Stoklasek TA, et al. (2006) Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol 177(9):6072-80 |
| abstractText | 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-15Ralpha to target cells expressing the IL-15Rbeta and the common gamma-chain. Thus, the efficacy of administered IL-15 alone may be limited by the availability of free IL-15Ralpha. We now show that administration of soluble IL-15/IL-15Ralpha 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-15Rbeta, but not IL-15Ralpha, expression by the responding cells and was IL-7-independent. Interestingly, IL-15/IL-15Ralpha 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. |
