Recombinant expression, downstream optimization, and therapeutic evaluation of recombinant human interleukin-37 for cancer therapy.

Abstract

Interleukin-37 is a cytokine with potent immunosuppressive properties that has been shown to have potential to treat autoimmune and chronic inflammatory diseases, as well as certain types of cancer. IL-37 is a 19kDa protein which interacts with proteins in receptor-dependent and receptor-independent pathways. The expression of the IL-37 protein cloned into the pET-28a vector was optimized in Rosetta 2(DE3) after comparing its expression with Rosetta-gami 2(DE3) and Rosetta 2(DE3) pLysS, which was then used for the large-scale production of IL-37. IMAC purification of IL-37 yielded > 97% pure 0.9mg/mL protein from auto-induced fermentation. The IC50 value of IL-37 was < 1µM, which was similar to that of doxorubicin, and proliferation of > 80% of all cancer cells was inhibited by 100µg/mL of IL-37 protein. IL-37 may be a promising theragnostic target for cancer due to its comparable IC50 value with that of doxorubicin.