MAPC® cell therapy enhances the ex-vivo expansion of polyclonal, regulatory T cells

Abstract

Background & Aim Regulatory T (Treg) cells are a naturally occurring population of lymphocytes that maintain immune homeostasis and resolve excessive immune activation. They act through a spectrum of cell-mediated and soluble mechanisms. Preclinical data in humanized mouse models has firmly established that adoptive transfer or in vivo generation of Treg cells can remedy autoimmunity, GVHD and solid organ transplant rejection; a few clinical trials have already demonstrated safety and suggest some limited efficacy. Therefore, clinical adoptive Treg cell therapy (the isolation, ex vivo expansion and re-infusion of Treg cells) has been heralded as a promising strategy for the treatment of auto-immune and inflammatory disorders. As such, a living drug cell therapy may have greater specificity and more complex therapeutic benefits than conventional immunosuppressive drugs and could potentially cure autoimmune diseases by restoring the immune tolerance. However, several major roadblocks in the widespread clinical implementation of Treg therapy remain, mainly the low number of Treg cells that can be harvested from peripheral blood (PB) and the limited expansion potential, while maintaining purity and function. Methods, Results & Conclusion ReGenesys has developed a platform technology for the expansion of Treg cells derived from PB while fully maintaining their functional characteristics. This platform is based on the use of our proprietary MAPC stromal stem cell therapy which consists of non-hematopoietic stem cells derived from bone marrow that secrete various growth factors and have potent immunomodulatory effects. When CD4+CD25+127low-sorted Treg cells from PB were expanded on MAPC cells, a robust and high Treg cell yield was obtained, reaching the critical threshold of clinical batch production (1 billion cells) in all donors. Furthermore, a higher purity was observed (less potential CD8+ T cell contamination) and a specific signature was seen in terms of phenotype (low skin-homing/ high gut-homing marker expression). The immunosuppressive function was confirmed in both in vitro and in vivo models. Finally, successful Treg expansions have also been performed from PB of Crohn's Disease patients.