Translational development of specialized NK cells for cancer immunotherapy

Project Summary Abstract The annual incidence of head and neck cancers worldwide is more thancases with arounddeaths each yearand it is estimated that inthere will benew cases of non Hodgkin lymphoma with an estimateddeaths this yearIn this proposalwe describe a strategy to use a novel subset of natural killer cellsg NK cellsallogeneically for cancer therapyWe hypothesize that expansion and adoptive transfer of g NK cellsconcurrent with a targeting therapeutic mAbwill result in clinically meaningful responses in vivoImportantlybecause adoptive transfer of NK cells in humans does not result in severe graft versushost diseaseGVHDlike reactions when given in an allogenic contextunlike adoptive T cells transferswe propose that this antibody directed NK cell therapy could be given in anoff the shelfmanner andas suchbe more broadly applicable for clinical useThe studies proposed in this application will establish the necessary expansion protocols and in vivo proof of concept results necessary for clinical development of this strategyIndapta TherapeuticsInc`Indaptaandaposhas entered into a relationship with the Stanford University to develop and test a next generation cancer therapyIndapta aims to become a leader in safe and effective cellular immuno oncology therapy by building on a novel discovery by professors from Stanford and UC DavisThey are confirming a unique synergy between monoclonal antibodiesmAbsand a specific and potent variety of `natural killerandaposNKimmune cell lacking the Fc RIadapterthe g NK cellThe scientific premise is that the conventional NK cells that have mutated after coming into contact with CMV to be lacking the Fc RIadapterG NKwill significantly increase ADCC and favorable apoptosis in the presence of a MAB to increase tumor killingThe product will combine these special g NK cells with a targeting mAbcetuximab for head and neck cancer and rituximab for lymphoma to destroy these cancer cells with high precision and efficacyIndapta owns the exclusive license to the patents protecting this technologyThe PI for this grant is DrJohn Sunwoo PhD in Immunology from StanfordThe CEO of Indapta has secured two NCI SBIR Fast Track grants and one Phaseb commercialization grant totaling $M for his first companywhich has attracted over $M in venture funding as it moves to commercialize its early stage technologyThe Stanford and UC Davis team include leaders in NK cell therapy and a translational scientist at UCSF with extensive expertise in preclinical NK cell modelsIndaptaandapos s productpairs g NK cells with mAbs cetuximab and rituximab to target head and neck and lymphoma cancersThis pairing enables us toiharness the high potency of g NK cellsiiidentify cancer cells by using a specialized mAbcetuximab and rituximabiiilower the risk of adverse immune responsea feature of genetically engineered immunotherapiesbecause g NK cells occur naturallyandivbenefit from the longevitymonthsof g NK cells as compared to conventional NK cellsweeksthereby reducing frequency of infusions as part of the immunologic regimen Project NarrativePublic Health RelevanceThe annual incidence of head and neck cancers worldwide is more thancases with arounddeaths each yearand it is estimated that inthere will benew cases of non Hodgkin lymphoma with an estimateddeaths this yearIn this proposalwe describe a strategy to use a novel subset of natural killer cellsg NK cellsallogeneically for cancer therapyWe hypothesize that expansion and adoptive transfer of g NK cellsconcurrent with a targeting therapeutic mAbwill result in clinically meaningful responses in vivoImportantlybecause adoptive transfer of NK cells in humans does not result in severe graft versushost diseaseGVHDlike reactions when given in an allogenic contextunlike adoptive T cells transferswe propose that this antibody directed NK cell therapy could be given in anoff the shelfmanner andas suchbe more broadly applicable for clinical useThe studies proposed in this application will establish the necessary expansion protocols and in vivo proof of concept results necessary for clinical development of this strategy