Significance: Intracellular delivery of nucleic acids to immune cells is an important component of many current and anticipated cellular therapies, including chimeric antigen receptor T Cell (CAR-T) therapies for the treatment of cancer. These therapies use immune cells called T cells, either from the patient themselves, or a healthy donor, and genetically engineer them to kill the tumor cells. The genetic engineering involves direct delivery of nucleic acids to these cells, which is challenging as current delivery methods either lack efficiency, are very damaging to cells, or both. This becomes a critical concern for strategies that either seek to perform multiple, sequential deliveries or aim to generate a large number of cells (1010) for development of an off-the- shelf therapeutic. OpenCell Technologies (OCT) has developed a proprietary technology, POROS?, to deliver macromolecules such as DNA, RNA and protein to a wide variety of cell types. POROS uses acoustic force to push cells through an array of nozzles one cell at a time thus creating shear force to porate cells. In this SBIR project, OCT will expand the capabilities of its POROS platform by developing higher through-put POROS devices. Background: CAR-T therapy is a rapidly emerging therapy for the treatment of cancer, with two companies recently receiving FDA approval for their first CAR-T therapies. The existing therapies involve using the patient?s own cells and engineering them to attack the tumor cells. This engineering is performed on a case-by- case basis and the methods are costly and time-consuming. In order to make CAR-T therapies available to more patients in a cost-effective, safe and timely manner, a new approach needs to be developed. Current research is addressing this need by engineering healthy donor T cells to be used in CAR-T therapy. However, methods and technology need to be developed to support this new approach, which will involve multiple gene- editing steps and on a much larger scale. Approach: In this Phase I feasibility study, OCT will demonstrate that its delivery technology, POROS, can be expanded to treat a larger number of cells to enable CAR-T development. In this project, we will develop a prototype POROS-midi device, capable of treating 108 cells in under 10 minutes, and demonstrate gene editing in T cells as a proof-of-concept experiment. While the POROS-midi device development will serve as a feasibility study for development of a large, all-in-one, GMP-compliant POROS-giga device, POROS-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 medicine. One such therapy for cancer, chimeric antigen receptor T cell (CAR-T) therapy, takes a patient?s own immune cells, or donor cells, and modifies them in such a way that they more effectively fight the cancer. Currently, these treatments are produced on a case-by-case basis and are very costly, time-consuming and technically challenging, which limits the ability for wide-spread use. The bottleneck is the cellular engineering, which requires delivery of macromolecules such as RNA to the T cells that are being modified, which is a challenging process. OpenCell Technologies (OCT) has 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 batch, thus providing the possibility of developing an off-the-shelf therapy. This 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 treated, while maintaining cell viability and recovery.
