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 such as CTLA4.

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 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 CytoSage Team have extensive Cell Therapy Development experience through over 30 years of research of anti-inflammatory cells therapy including phase 1 to 3 clinical trials in trauma, stroke and examination biomarker profiles in some of the associated secondary co-morbidities including ARDS and kidney disease.

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.