Novel Immuno-oncology Strategy for Targeted Cytotoxic Lymphocyte Activation

PROJECT SUMMARY ABSTRACT Systemic administration of high dose ILhas been used since thes as an FDA approved immunotherapy for metastatic cancerDespite the fact that up toof patients treated with high dose ILachieve a durablelong term responsethis therapy is rarely used today due to significant life threatening complicationsSuch complications occur due to ILactivation of vascular endotheliumresulting in systemic capillary leakas well as other adverse effects associated withoff targetsignaling of ILIn additionILpreferentially activates CDFoxpregulatory T cells that mitigate the tumor specific responseWe recently published an ILfusion protein which targets and solely activates cytotoxic T lymphocytes in the absence of endothelial or regulatory T cell activationIn addition to a dramatically increased safety profileour ILfusion protein inhibits the growth of highly aggressive tumors normally resistant to other forms of immunotherapyThe purpose of the current proposal is to evaluate the immunogenicity of this proteinexplore its clinical response when used in combination with checkpoint blockade immunotherapyand evaluate its utility for expansion of tumor reactive leukocytes for adoptive cell therapySuccessful completion of the proposed studies will support a Phase II STTR application and eventually advancement of this therapy to IND enabling studiesOur ultimate goal is to submit this novel immunotherapy to the FDA for first in human clinical safety trials PROJECT NARRATIVE Patients with advanced cancerssuch as lung cancerhave few treatment options with limited long term survivalFDA approved high dose ILtherapy leads to a high rate of long term durable remissions in several malignanciesbut is infrequently utilized due to high rates of therapy associated morbidity and mortalityCourier Therapeutics has developed a targeted form of ILwhich dramatically reduces the adverse effects of ILtherapy while enhancing therapeutic efficacyThese studies will support future submission of this novel therapeutic agent to the FDA for a lung cancer human clinical trial