Single Cell CytoScreen: An Imaging Platform for Evaluating Drug Combination Efficacy and Resistance in Individual Cancer Patients

Project Summary CytoImage Dx in collaboration with OHSU will establish a commercial platform technology that offers unprecedented molecular level sensitivityincreased multiplexing capabilityand minimized patient sample requirementthereby providing functional profiling of increased numbers of drug combinations with improved single cell granularityThis will help accelerate target pathway identification of synergistic compounds most effective in killing cancerous cells while minimizing drug resistant minor cell subpopulationsCurrent flow cytometry platforms query cell identity but are sample limited todrug combination agents and do not offer reliable measures of keyclinically relevant proteinse gphosphoproteinsthat are challenging to detect in single cellsdue to their low basal levelsThusmany drug targets and patient samples cannot be evaluated and the absence of protein detection cannot be reliably interpreted as a negative resultOHSU has built an imaging platform addressing these technical bottlenecks that is currently used in NCI sponsored projects to screen patients enrolled in Beat AMLthe world s most comprehensive AML cohort to date that is nominating imuno onc small molecule drug combinations for acute myeloid leukemia to clinical trialsWe have shown that the platform identifies small molecule immune checkpoint inhibitor combinations that more effectively induce leukemia cell kill and immune cell proliferationThe platform requires xfold less patient sample sizemaking feasible the evaluation of expanded drug combinations and functional characterization of targeted pathways and individual cells cell subtypese gT cellleukemic cellProprietary super localization algorithms discriminate discrete protein complexes tagged with antibody fluorophore probesoffering up to xtimes increased signal to noise over flow cytometry and fluorescence microscopyJacob et alSci Reportspatents issuedpendingenabling reliable detection of drug resistant progenitor cellsIn this SBIR Phase I applicationwe propose to benchmark platform performance to obtain CLIA forward specs necessary for commercializationto enhance the multiplexing capability beyond current state of the artand to profile targeted pathways and cell subpopulations responding to small molecule immune checkpoint inhibitor combinations that produce the most effective tumor cell kill T cell proliferationwhile minimizing residual phosphoactivedrug resistant cellsThis would allow Phase II focus in testing in expanded patient cohortsThe collaborative team consists of innovators of the single cell imaging platformclinicianscientists leading efforts to identify leukemia targeted therapeutics for clinical deploymentand an executive in residence with a track record of fostering successful start upsCytoImage Dx has an option agreement to exclusively license the OHSU platform technologyLetters of support attest to the innovationclinical significanceand institutional support of the technology for commercial spin out Project Narrative We will commercialize a state of the art single cell imaging platform to evaluate the effectiveness of drug combinations in individual leukemia patient blood samplesThe platform offers new molecular ultrasensitivityincreased multiplexing capabilityand minimized patient sample requirementthereby providing functional profiling of increased numbers of drug combinations with improved single cell granularityThis technology has the potential to significantly improve patient therapeutic outcome by accelerating target pathway identification of synergistic drug combinations that are most effective in providing durable eradication of persistent cancer cells in individuals