CAR-T cell therapies targeting encephalitogenic myeloid cells in neuroinflammation
Novel CAR-T cell platform designed to selectively eliminate disease-driving bone marrow-derived myeloid cells in the central nervous system. Based on proprietary transcriptomic and epigenomic signatures distinguishing pathogenic myeloid subsets from protective microglia, enabling targeted treatment of multiple sclerosis and other neuroinflammatory disorders.
Overview
This research program develops antigen-specific cellular therapies using chimeric antigen receptor (CAR) T cells to precisely eliminate encephalitogenic bone marrow-derived myeloid cells that drive neuroinflammation and neurodegeneration in the central nervous system (CNS). The approach addresses a critical gap in treating multiple sclerosis (MS) and related neuroinflammatory and neurodegenerative disorders by targeting the specific myeloid cell subsets responsible for disease progression while sparing beneficial tissue-resident microglia.
The technology leverages proprietary molecular markers identified through single-cell transcriptomic and epigenomic profiling that distinguish pathogenic bone marrow-derived myeloid cells from protective CNS-intrinsic microglia. By focusing on surface-expressed molecules with confirmed cellular specificity, the platform enables the design of CAR-T cells with excellent CNS bioavailability and the potential for durable therapeutic effects.
Technical specifications
Key scientific foundations:
- Single-cell transcriptomic and epigenomic signatures differentiate myeloid cell subsets within the inflamed CNS based on ontogeny (yolk sac-derived microglia versus bone marrow-derived myeloid cells)
- Differential chromatin accessibility at specific loci reveals subset-specific biological pathways perturbed during inflammation
- Validated in the experimental autoimmune encephalomyelitis (EAE) model of MS, with confirmed relevance through human autopsy studies showing reduced myeloid cells in natalizumab-treated MS patients
CAR-T cell engineering approach:
- Chimeric antigen receptors generated by fusing molecule-specific antibody single-chain variable fragments (scFvs) via transmembrane linker domains to the CD3ζ chain of the T cell receptor
- Construct transfection into α/β T cells followed by established activation and expansion protocols
- In vitro and in vivo depletion assays to validate target cell elimination
Target prioritization criteria:
- Protein turnover characteristics
- Overall cellular specificity
- Surface expression profile
Technology readiness level
The program is currently at preclinical validation stage, building on published transcriptomic and epigenomic characterization of myeloid cell subsets in CNS autoimmunity. Prior work has demonstrated proof-of-concept for distinguishing pathogenic myeloid populations using molecular markers, and ongoing efforts are verifying these targets through proteomic analyses. CAR-T cell constructs are being generated and will undergo both in vitro and in vivo depletion assays to confirm efficacy. Future work will advance toward translational studies to evaluate therapeutic potential in neuroinflammatory disease models.
About University of Texas Southwestern Medical Center
UT Southwestern Medical Center is a leading academic medical center within the University of Texas System, combining biomedical research, education, and a major clinical enterprise in Dallas. Co-located hospitals and outpatient networks provide direct access to clinicians, diverse patient populations, and real‑world data, enabling rapid design and execution of clinical studies. Companies engage through on‑campus incubator space, shared core facilities, and collaboration models that range from sponsored research to multi‑site trials. Research is supported primarily by NIH, with additional competitive federal awards from other national agencies. A dedicated technology transfer office streamlines IP protection, licensing, and startup formation to accelerate commercialization.
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