STTR Phase I: Developing an optical metabolic flow cytometer to screen T cell fitness for Chimeric Antigen Receptor (CAR) T-cell Therapy

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is a rapid diagnostic method for identifying patients that will benefit from Chimeric Antigen Receptor (CAR) T cell therapy. Chimeric Antigen Receptor T cell therapy is an emerging clinical method of producing lasting remission in cancer patients by re engineering patient’s own T cells. The therapy also remains under active investigation for other emerging applications. The T cells in nearly half of cancer patients eligible for CAR T cell therapy are not sufficiently healthy to be successfully manufactured into viable and effective CAR T cells for use as intended. This leads to CAR T cell manufacturing failures for 15-69% of patients, resulting in a significant burden to the health care system with an estimated cost of $375k per patient along with increased risks to patient morbidity and severe adverse events. The system aims to be the first to correlate specific quantifiable energy measures with CAR T cell manufacturing failure risks. If successful this new screening method would provide a high throughput system capable of identifying patients at high risk for CAR T cell manufacturing failure with reduced time, labor for optimization and reagent validation than current methods. This would allow patients to pursue other clinical options sooner rather than undergoing ineffective CAR T therapy thereby enabling them to see alternative viable options sonner while reducing unnecessary health care resource utilization. This Small Business Innovation Research (SBIR) Phase I project will develop a novel instrument for assessing the health of Chimeric Antigen Receptor T cells before undergoing the isolation and modification process for oncological therapeutic use. The novel technology monitors the energy production of T cells indicative of health and viability. The Phase I project aims to develop and validate a reproducible flow cell analyzer prototype capable of operating in a continual flow pass through manner. The first phase includes design engineering and development of optical components, algorithms and external components utilizing their proprietary approach. The second phase will provide prelininary experimental validation in human test samples. These results will demonstrate the feasibility of a clinical diagnostic prototype and serve as proof of concept for developing a human grade system at a future stage. 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.