Innovative ABC AND Gate CAR T Therapy for Autoimmune Disorders

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/WO2025250591A1

Related 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