Establishing the POROS Intracellular Delivery System as a Platform for Cellular Therapeutics

Abstract SignificanceIntracellular delivery of nucleic acids to immune cells is an important component of many current and anticipated cellular therapiesincluding chimeric antigen receptor T CellCAR Ttherapies for the treatment of cancerThese therapies use immune cells called T cellseither from the patient themselvesor a healthy donorand genetically engineer them to kill the tumor cellsThe genetic engineering involves direct delivery of nucleic acids to these cellswhich is challenging as current delivery methods either lack efficiencyare very damaging to cellsor bothThis becomes a critical concern for strategies that either seek to perform multiplesequential deliveries or aim to generate a large number of cellsfor development of an off theshelf therapeuticOpenCell TechnologiesOCThas developed a proprietary technologyPOROSto deliver macromolecules such as DNARNA and protein to a wide variety of cell typesPOROS uses acoustic force to push cells through an array of nozzles one cell at a time thus creating shear force to porate cellsIn this SBIR projectOCT will expand the capabilities of its POROS platform by developing higher through put POROS devicesBackgroundCAR T therapy is a rapidly emerging therapy for the treatment of cancerwith two companies recently receiving FDA approval for their first CAR T therapiesThe existing therapies involve using the patient s own cells and engineering them to attack the tumor cellsThis engineering is performed on a case bycase basis and the methods are costly and time consumingIn order to make CAR T therapies available to more patients in a cost effectivesafe and timely mannera new approach needs to be developedCurrent research is addressing this need by engineering healthy donor T cells to be used in CAR T therapyHowevermethods and technology need to be developed to support this new approachwhich will involve multiple geneediting steps and on a much larger scaleApproachIn this Phase I feasibility studyOCT will demonstrate that its delivery technologyPOROScan be expanded to treat a larger number of cells to enable CAR T developmentIn this projectwe will develop a prototype POROS midi devicecapable of treatingcells in underminutesand demonstrate gene editing in T cells as a proof of concept experimentWhile the POROS midi device development will serve as a feasibility study for development of a largeall in oneGMP compliant POROS giga devicePOROS midi will also be a salable unit of its own with anticipated applications in personalized medicine and research and development Establishing the POROS intracellular delivery system as a platform for cellular therapeutics Project Narrative Cellular therapeutics are rapidly emerging as an exciting new area in cancer therapy and regenerative medicineOne such therapy for cancerchimeric antigen receptor T cellCAR Ttherapytakes a patient s own immune cellsor donor cellsand modifies them in such a way that they more effectively fight the cancerCurrentlythese treatments are produced on a case by case basis and are very costlytime consuming and technically challengingwhich limits the ability for wide spread useThe bottleneck is the cellular engineeringwhich requires delivery of macromolecules such as RNA to the T cells that are being modifiedwhich is a challenging processOpenCell TechnologiesOCThas developed a delivery technology very different from the current leading technology that is gentler on the cells and can be used to treat a larger number of cells in a single batchthus providing the possibility of developing an off the shelf therapyThis feasibility project will test the inherent scalability of OCT s delivery technology by developing and demonstrating that the novel continuous flow system will allow for treatment of a much larger number of cells than currently treatedwhile maintaining cell viability and recovery