Thymic Regulatory T cells - Allogeneic Treatment of Acute Immune-Inflammatory Conditions

Regulatory T lymphocytes (‘Tregs’) provide the brake on excessive immunity and inflammation within the immune system and provide a route for resolution of immune and inflammatory responses. They mediate these functions through actions at lymphoid tissue, such as lymph nodes and in the periphery at inflammatory sites. Tregs utilize several mechanisms for conduct of immunomodulation including the release of very potent mediators including IL-10 and TGF beta, their activation through IL-2 and direct cell-cell contact through inhibitory surface receptors.

A rich source of Tregs is the thymus. Human thymus tissue is accessible as a disposed biproduct of cardiovascular surgery in infants. Infant thymus-derived Tregs have also demonstrated relatively longer immunomodulatory activity in allogeneic transplantation. Infant thymus Tregs also have a relatively greater capacity for expansion for the purpose of cell bank generation; routinely undergoing a 1000-fold expansion from a starting point of 1 billion cells within several weeks of culture. With Treg therapy generally considered to require in the region of 1 billion cells per administration, this presents a capacity for generation of up to 1000 treatments per disposed thymus.

The Texas Medical Center cell therapy infrastructure circumvents several of the barriers to market entry of a Treg product. The center has a significant patient population with a broad genetic background, assisting generation of a diverse cell bank for HLA matching. The center also has an established relationship with the cardiovascular surgery department for thymus tissue access. As important from a regulatory context, the center has established a new cGMP cell therapy production suite adjacent to the cardiovascular operating room, providing access to approximately 250 cardiovascular surgery-derived thymus cases per year.

MSC experience

Disease Stratification Through Blood Proteomics and Multivariate Statistics

CytoSage benefits from licensed cutting edge proprietary proteomic technology from Aeirtec, patented issued in the USA, EU and China. The assay technology incorporates ultra high assay sensitivity within blood marker multiplexing that avoids loss of data on top of the hierarchy markers that exist in low abundance. CytoSage members have extensive experience in coupling this technology to application of multivariate analysis for interpretation of multiple marker data. Through this route, CytoSage members have previously established marker relationships with immune aspects of ARDS, Stroke and autoimmune disease. Within both autoimmune and dermatological disease they have also established marker profiles of treatment responders and nonresponders (Spencer et al., 2025), but also in the context of the current stratification direction, profiles providing prediction of therapeutic response.

Immunopharmacology applied in regulatory QC of anti-inflammatory action potency screening

Development and clinical application of a regulatory T cell therapy requires a platform of quality control including ‘potency screening assays’ for ongoing confirmation of the efficacy and potency of the cell product. The CytoSage Team’s capacity for development of an immunomodulatory and anti-inflammatory cell therapy product is matched by their experience in monitoring the potency and efficacy of anti-inflammatory agents against human adaptive and innate immune cell function. Specifically, they have extensive experience in isolation of human immune and inflammatory cell types and monocyte progression to antigen presenting dendritic cells or M1/M2 macrophages. They have utilized this capacity for subsequent monitoring the efficacy and potency of anti-inflammatory agents under development against lymphocyte function, antigen presentation by dendritic cells and the inflammatory actions of neutrophils and macrophages. In addition to cutting edge proteomics multiplexing technology, CytoSage have state of the art cellular imaging systems, multicolor flow cytometry and next generation sequencing (NGS) for monitoring of critical signature indices of regulatory T cell immunomodulatory and anti-inflammatory activity.