Synergistic Anti-tumor Efficacy of an Interleukin 2 Analog and PD-1 blockade

Principal Investigator Program DirectorLastFirstMiddleChenRidong Abstract The durable clinical efficacy of immune checkpoint inhibitors in a variety of cancers has demonstrated the tremendous potential of tumor immunotherapyHowevercurrent approaches are limited to immunogenic tumors that acquire adaptive resistanceInterleukinILimmunotherapy can result in remarkable long term responses in some cancer patients by stimulating the immune response to kill tumor cellsHowevercurrent rILtherapy is limited to highly selected patients due to its requirements for high and frequent dosingwhich results in severe side effectsMoreoverrILalso activates CDregulatory T cellswhich suppress the immune responseTo ameliorate the liabilities of the current rILdrugwe have designed a long acting ILanalog that selectively preserves immune response activationCDTNK cellswithout activating regulatory T cells and endothelial cellstherebyminimizing immune suppression and vascular leak syndromeWe also propose to optimize combination rILanalog treatment plus checkpoint therapy in order to safely and effectively kill tumor cells by simultaneously activating anti tumor pathways of the immune system and removing inhibitory mechanismsIn this studythe Specific Aim is to use a syngeneic BFmouse model to determine whether the combination of the proprietary ILanalog with checkpoint therapyPDblockadeis more effective in eradicating tumors without increasing side effectsOur long term goal is to develop the proprietary ILanalog as a safe immunotherapy to cure cancer or extend survival of patients Principal Investigator Program DirectorLastFirstMiddleChenRidong NarrativeWe will determine whether combination treatment of the proprietary rILanalog plus checkpoint therapy safely and more effectively kill tumor cells than either monotherapy