Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model

Journal for ImmunoTherapy of Cancer

Christopher J. Paige¹  Caren L. Furlonger¹  Joshua M. Moreau¹  Jeffrey A. Medin¹  Sarah J. Colpitts¹  Maura B. Bendix¹  Melanie S. S. Seabrook¹  Alexandra Berger¹  William M. McKillop¹ 

[1] Princess Margaret Cancer Centre, University Health Network;

关键词: Leukemia;    Interleukin-15;    Cancer immunotherapy;    T-cells;    NK-cells;   

DOI  :  10.1186/s40425-019-0777-8

来源: DOAJ

【 摘 要 】

Abstract Cytokines of the common γ-chain receptor family such as IL-15 are vital with respect to activating immune cells, sustaining healthy immune functions, and augmenting the anti-tumor activity of effector cells, making them ideal candidates for cancer immunotherapy. IL-15, either in its soluble form (IL-15sol) or complexed with IL-15Rα (IL-15Rc), has been shown to exhibit potent anti-tumor activities in various experimental cancer studies. Here we describe the impact of intraperitoneal IL-15 in a cancer cell-delivered IL-15 immunotherapy approach using the 70Z/3-L leukemia mouse model. Whereas both forms of IL-15 led to significantly improved survival rates compared to the parent cell line, there were striking differences in the extent of the improved survival: mice receiving cancer cells secreting IL-15sol showed significantly longer survival and protective long-term immunity compared to those producing IL-15Rc. Interestingly, injection of leukemia cells secreting IL-15sol lead to heightened expansion of CD4+ and CD8+ T-cell populations in the peritoneum compared to IL-15Rc. Cell-secreted IL-15Rc resulted in an influx and/or expansion of NK1.1+ cells in the peritoneum which was much less pronounced in the IL-15sol model. Furthermore, IL-15Rc but not IL-15sol lead to T-cell exhaustion and disease progression. To our knowledge, this is the first study detailing a significantly different biological effect of cell-delivered IL-15sol versus IL-15Rc in a mouse cancer immunotherapy study.

【 授权许可】

Unknown