Abstract: The present disclosure relates a modified interleukin 18 (IL-18) polypeptide comprising a polymer, 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 half-a maximal effective concentration (EC50) to induce IFN? production is a cell lower than the EC50 of wild type IL-18 (WT IL-18). The modified IL-18 polypeptide can exhibit superior tumor growth inhibition properties and increased half-life in plasma compared to an identical IL-18 polypeptide with no polymer attached. The modified IL-18 polypeptide can also include an optimally sized polymer attached for enhanced efficacy.

Abstract: The present disclosure relates to bifunctional cytokine compositions comprising first and second cytokines connected by a linker, as well as methods of making bifunctional cytokine compositions. The disclosure also relates to bifunctional cytokine compositions comprising interleukins, including interleukin-2, interleukin-7, and interleukin-18, as well as derivatives thereof.

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.