SBIR Phase I: Isolating and Reformatting Immune Receptors into Targeting Therapies for Oncology, Auto-Immunity, and Infectious Diseases

The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase I project will be in the creation of new drugs to treat life-altering diseases. Despite leaps in medical technology, the world still grapples with infectious disease, cancer, and auto-immune disease. Auto-immune conditions and allergies are on the rise along with some types of cancers-particularly in young adults (e.g. colorectal cancers). The field needs new disease-specific targets that can be leveraged by current and next-generation therapeutic approaches. To achieve this goal, technologies to discover those disease-relevant targets and ways to exploit them in patients are essential. Among these targeting tools are T-cells: immune cells that are critical in the body’s defense against viral and bacterial infections as well as cancer. This SBIR project focuses on the development of a platform for isolating T-cells specific to disease and a process which will take disease-specific T-cell receptors and convert them to a druggable, widely accessible format. Together, these two platforms may provide a system for mining diseases to develop a sustainable pipeline of new therapies. These therapies would contribute to the $200B oncology market, the $72B auto-immune market, and the $70B infectious disease market. The proposed project is focused on a method to discover drugs against new targets and a method to convert those potential drugs into therapeutics. This SBIR project aims to develop a unique method of isolating disease-relevant T-cells. Tens of millions of different T-cells will be co-cultured with diseased cells in microscopic compartments. T-cells that recognize the diseased cells are “activated”. These activated cells will be identified and isolated to recover their associated disease-specific receptors. Specifically, the work here will focus on isolating rare, disease-reactive T-cell receptors (TCRs) from large pools of human T-cells: a step that is critical for the technology to be exploited for drug discovery against new targets. However, the TCRs that are encoded by the isolated T-cells are naturally expressed on the surface and are not fit for making adaptable, affordable, and easy-to-manufacture therapeutics. This SBIR project will also strive to format these TCRs into a therapeutic modality that is manufacturable and deliverable to patients. These methods will leverage the latest in drug design technologies such as the use of artificial intelligence and high-throughput optimization. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.