{"id":"06698","slug":"innovative-abc-and-gate-car-t--06698","source":{"id":"06698","dataset":"techtransfer","title":"Innovative ABC AND Gate CAR T Therapy for Autoimmune Disorders","description_":"<p>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.</p><p><h2>Description</h2>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.</p><p><h2>Applications</h2>•\tTreatment of autoimmune diseases such as SLE, RA, MS, and Ankylosing Spondylitis\r<br>•\tPotential use in other diseases associated with ABC B cells</p><p><h2>Advantages</h2>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.</p><p><h2>Invention Readiness</h2>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.</p><p><h2>IP Status</h2><a target=\"_blank\" href=\"https://patents.google.com/patent/WO2025250591A1\">https://patents.google.com/patent/WO2025250591A1</a></p><p><h2>Related Publication(s)</h2><p>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., &amp; Shlomchik, M. J. (2023). Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice. Journal of Experimental Medicine, 220(5). <a target=\"_blank\" href=\"https://doi.org/10.1084/jem.20221346\">https://doi.org/10.1084/jem.20221346</a></p></p>","tags":["Autoimmune"],"file_number":"06698","collections":[{"key":513,"name":"Cell & Gene Therapy"}],"meta_description":"Engineered AND-gate CAR T cells selectively deplete age-associated B cells, targeting autoimmune diseases while sparing healthy cells.","image_url":"","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":2.0,\"scalability\":3.0,\"timeliness\":4.0},\"weighted_score\":0.25,\"risks\":[\"Readiness/TRL is low (TRL 1) with mainly in vitro/mouse data; manufacturing and safety validation needed.\",\"Biological/therapeutic risk: dual-AND gate CAR may have off-target or insufficient activation; potential immunogenicity of synthetic CARs.\",\"Regulatory/pathway uncertainty for autoimmune indications; patient selection and safety concerns (autoimmunity risk).\"],\"one_sentence_take\":\"High novelty and potential impact with a promising AND-gate design, but readiness is early (TRL 1) and significant development, safety, and regulatory hurdles remain before clinical translation.\"}","lead_inventor_name":"Jason Lohmueller","lead_inventor_dept":"Med-Surgery","technology_type":"Therapeutic Modality","technology_subtype":"Cell Therapy - T Cell","therapeutic_areas":["Neuroscience","Immunology"],"therapeutic_indications":["Multiple Sclerosis (MS)"],"custom_tags":[],"all_tech_innovators":["Jason Jakob Lohmueller","Mark Jay Shlomchik"],"date_submitted":"2024-03-24","technology_readiness_level":"1. Research idea"},"highlight":{},"matched_queries":null,"score":0.0}