University of Pittsburgh researchers have developed a novel type of Chimeric Antigen Receptor (CAR) T cell therapy that targets Age-associated B Cells (ABC) using synthetic signaling. This innovative approach selectively depletes pathogenic B cells associated with autoimmune diseases such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Multiple Sclerosis (MS), while sparing healthy B cells and dendritic cells. This targeted therapy has the potential to improve treatment outcomes and reduce immunosuppression-related side effects.
Description
The technology involves the creation of synthetic CAR T cells that carry both CD19 and CD11c recognition domains, each linked to a partially defective signaling domain. This dual recognition system, known as an "AND" gate, ensures that only B cells expressing both CD19 and CD11c are targeted and eliminated. This selective depletion of ABCs, which are implicated in various autoimmune diseases, is achieved without affecting naive B cells or dendritic cells. The CAR T cells are designed with specific protein domains to ensure precise targeting and activation, leading to the effective elimination of pathogenic B cells.
Applications
• Treatment of autoimmune diseases such as SLE, RA, MS, and Ankylosing Spondylitis
• Potential use in other diseases associated with ABC B cells
Advantages
This technology selectively targets pathogenic B cells, reducing the risk of immunosuppression and associated safety concerns. The dual recognition "AND" gate system ensures precise targeting, improving the efficacy of CAR T cell therapy in autoimmune diseases. This approach has the potential to treat a wide range of autoimmune conditions currently lacking effective CAR T cell treatments.
Invention Readiness
The concept has been defined, and DNA sequences encoding the receptors have been designed. Researchers are constructing these receptors to test in both mouse and human T cells. The project is supported by start-up funds, with plans to apply for additional funding to obtain proof-of-concept preclinical data in vitro and in vivo.
IP Status
https://patents.google.com/patent/WO2025250591A1Related Publication(s)
Nickerson, K. M., Smita, S., Hoehn, K. B., Marinov, A. D., Thomas, K. B., Kos, J. T., Yang, Y., Bastacky, S. I., Watson, C. T., Kleinstein, S. H., & Shlomchik, M. J. (2023). Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice. Journal of Experimental Medicine, 220(5). https://doi.org/10.1084/jem.20221346
