SBIR Phase I: A single-cell-interaction platform for accelerating discovery of bispecific T-cell engagers

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be a platform to identify new immunotherpeutics for the treatment of cancer. For a variety of human diseases, cancer in particular, several recently approved immunotherapeutics can effectively treat and, in some cases, cure several forms of cancer that were considered fatal. Unfortunately, there are only a handful of these treatments currently available, and the cost is high. This project aims to develop a new technology that may empower biopharma and biotech companies to discover next generation therapeutics in an expeditious and cost-effective manner with a much higher chance of success. Ultimately, the project aims to help bring more efficacious and more affordable choices for immunotherapeutics to benefit patients with unmet medical needs. This SBIR Phase I is a proposal to evaluate a cutting-edge single-cell-interaction platform technology for its potential to accelerate the discovery of immunotherapeutics, specifically, the bispecific T cell engagers (BiTEs), a clinically validated class of bispecific antibodies. BiTEs consist of two distinct domains that can simultaneously bind to a T cell target and a tumor target. BiTEs' unique ability to link T cells to tumor cells allows them to exhibit improved specificity and efficacy, in part through a novel mode of action, by activating T cells to kill tumor cells. However, the development process for BiTEs has been very slow, limiting their clinical availability for a broad range of devastating diseases. A recurring challenge in the field is the lack of a robust platform that is capable of rapid and efficient identification of lead BiTE candidates in a cost-effective manner. The current proposal aims to prove the technical and operational feasibility of the proposed microfluidic-based single-cell-interaction platform technology that can directly interrogate the functions of many individual BiTE variants in a compartmentalized assay format. 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.