SBIR Phase I: Novel Protein-Based Platform for In Vivo Chimeric Antigen Receptor (CAR) Generation

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to expand access to advanced immune therapies by developing a new, protein-based approach that avoids genetic modification of cells. Current engineered immune cell treatments can cost hundreds of thousands of dollars per patient, require specialized manufacturing facilities, and involve complex, patient-specific processing. This project seeks to enable a more scalable and potentially lower-cost alternative by using manufactured proteins that can be administered directly and temporarily program immune cells inside the body. By leveraging established protein production methods, this approach could reduce manufacturing barriers and increase availability in community hospitals and resource-limited settings. The technology has potential applications in cancer, autoimmune diseases, and emerging infectious diseases, representing large and growing markets in need of safer and more accessible therapies. If successful, this project could support a new class of immune treatments that are more affordable, more rapidly developed for new disease targets, and more broadly distributed across the United States and globally. This Small Business Innovation Research (SBIR) Phase I project will evaluate a modular protein platform that enables immune cells to recognize and eliminate disease targets without altering their genes. Instead of inserting genetic material into cells, the project delivers pre-formed targeting proteins that attach to natural immune cells and temporarily give them new targeting abilities against diseased cells. The research will test whether this platform can be systematically adapted to different disease targets by swapping one targeting component for another while preserving overall function. Specifically, the project will design and produce a new version of the protein directed at a well-established immune cell target involved in autoimmune disease, then assess its structural stability, ability to bind the intended target, and capacity to activate immune cells to selectively eliminate harmful cells. Comparative studies across multiple versions of the protein will be used to establish general design principles that predict performance. The anticipated results include validated evidence of modularity, defined performance benchmarks, and a framework to guide future development of non-genetic immune therapies. 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.