Document Type
Article
Publication Date
7-4-2017
Abstract
Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number of CD8+ T cells (specifically CD44+ memory/activated phenotype) and NK cells. Intracellular IFN-γ and TNF-α secretion by CD8+ T cells increased in the IL-15SA-treated group. IL-15SA also upregulated NKG2D expression on CD8+ T cells. Moreover, IL-15SA enhanced proliferation and cytokine secretion of adoptively transferred CFSE-labeled T cells in syngeneic and allogeneic models by specifically stimulating the slowly proliferative and nonproliferative cells into actively proliferating cells.We then evaluated IL-15SA's effects on anti-tumor activity against murine mastocytoma (P815) and murine B cell lymphoma (A20). IL-15SA enhanced graft-versus-tumor (GVT) activity in these tumors following T cell infusion. Interestingly, IL-15 SA administration provided GVT activity against A20 lymphoma cells in the murine donor leukocyte infusion (DLI) model without increasing graft versus host disease. In conclusion, IL-15SA could be a highly potent T- cell lymphoid growth factor and novel immunotherapeutic agent to complement stem cell transplantation and adoptive immunotherapy.
Recommended Citation
Bailey, Cavan P; Budak-Alpdogan, Tulin; Sauter, Christopher T; Panis, Michelle M; Buyukgoz, Cihangir; Jeng, Emily K; Wong, Hing C; Flomenberg, MD, Neal; and Alpdogan, Onder, "New interleukin-15 superagonist (IL-15SA) significantly enhances graft-versus-tumor activity." (2017). Department of Medical Oncology Faculty Papers. Paper 68.
https://jdc.jefferson.edu/medoncfp/68
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
PubMed ID
28574833
Comments
This article has been peer reviewed. It was published in: Oncotarget.
Volume 8, Issue 27, 2017, Pages 44366-44378.
The published version is available at DOI: 10.18632/oncotarget.17875
Copyright © Cavan P. Bailey et al.