Electrotransfer of IL-15/IL-15Rα complex for the treatment of established melanoma
نویسندگان
چکیده
Background Interleukin-15 (IL-15) mediates the function of some innate and adaptive immune cells, which makes it an attractive target as an anti-cancer agent. Gene electrotransfer (GET) has been used to safely deliver plasmid DNA (pDNA) to tissues in a number of pre-clinical and clinical studies for cancer therapy. Previously we have shown using GET to deliver interleukin-15 (IL-15) to mouse melanoma resulted in long term-tumor regression and survival of a percentage of treated animals after challenge. Here we aim to improve this protection by modulating the levels of IL-15 expressed and stabilizing the protein by co-expressing its soluble receptor IL-15Ra.
منابع مشابه
Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum.
IL-15 is an important cytokine for the function of the immune system, but the form(s) of IL-15 produced in the human body are not fully characterized. Coexpression of the single-chain IL-15 and the IL-15 receptor alpha (IL-15Rα) in the same cell allows for efficient production, surface display, and eventual cleavage and secretion of the bioactive IL-15/IL-15Rα heterodimer in vivo, whereas the s...
متن کاملMHC class I and TCR avidity control the CD8 T cell response to IL-15/IL-15Rα complex.
IL-15 operates via a unique mechanism termed transpresentation. In this system, IL-15 produced by one cell type is bound to IL-15Rα expressed by the same cell and is presented to apposing cells expressing the IL-15Rβ/γC complex. We have shown that administering soluble IL-15Rα complexed with IL-15 can greatly enhance IL-15 activity. We now show that the naive CD8 T cell response to exogenous IL...
متن کاملMHC Class I and TCR Avidity Control the CD8 T Cell Response to IL-15/IL-15Rα Complex
IL-15 operates via a unique mechanism termed transpresentation. In this system, IL-15 produced by one cell type is bound to IL-15Rα expressed by the same cell and is presented to apposing cells expressing the IL-15Rβ/γC complex. We have shown that administering soluble IL-15Rα complexed with IL-15 can greatly enhance IL-15 activity. We now show that the naive CD8 T cell response to exogenous IL...
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