Abstract: The present disclosure relates to activatable proteins which comprise cleavable moieties attached thereto which display an altered activity upon cleavage of the cleavable moieties. The present disclosure also relates to activatable IL-2 polypeptides which comprise cleavable moieties, as well as compositions and methods of use thereof. The present disclosure further relates to cleavable peptides which can be cleaved by multiple proteases, as well as to polypeptides incorporating said cleavable peptides.

Abstract: The present disclosure relates a modified interleukin 18 (IL-18) polypeptide, methods of making the same, and methods of using the modified IL-18 polypeptides for treatment of diseases including cancer. The modified IL-18 polypeptide can exhibit an ability to induce interferon gamma (IFN?) production when in contact with a cell, exhibit a diminished ability to be inhibited by IL-18 binding protein (IL-18BP) compared to wild type IL-18 (WT IL-18), and exhibit a ratio of half-maximal inhibitory concentration (IC50) by IL-18BP to half-maximal effective concentration (EC50) to induce IFN? production which is greater than that of WT IL-18.