Harnessing Nature to Reverse Inflammation.



Immune responses consist of a period of inflammation, during which diseased tissue or invading organisms are eliminated. This causes variable damage within the embattled region, which must then be repaired. The immune system has evolved such that it exercises both inflammatory and reparative functions. These distinct "polarities" are established during early development and maintained throughout life. In autoimmune disorders, these functions are thrown out of balance, being biased towards inflammation and lacking repair.



Independent investigations have revealed the ability of the anti-inflammatory network to reverse autoimmunity. This network includes subsets of T-cells (regulatory T cells, or "Treg"), M2 macrophages and cDC2A dendritic cells (collectively, antigen presenting cells or "APC"). These cells can be (and have been) isolated from patients and their activities modified, but this is at best a difficult task due to the paucity of desired cells in the human body. Regenerative medicine enables a revolutionary approach being driven by ProxyKine - the production of a synthetic immune system that integrates properties necessary to impinge upon, and reverse, autoimmune inflammation. 



Our objective is production of a recombinant synthetic immune system designed to shut down inflammation and enable repair of the damaged tissue. The overarching attributes will include first-responders (APC) that will initiate the repair and call upon Tregs to further enforce immune suppression. With inflammation controlled, the system will be primed for regeneration of the damaged tissue (examples would include pancreatic beta cells for a person living with Diabetes and myelinating schwann cells for those afflicted with Multiple Sclerosis). All of these cellular actors will be created and enabled using human induced pluripotent stem cells.  



Our synthetic immune system will include modifications facilitating antigen-specific interactions between Tregs and the regenerative tissue they will protect, as well as the APC that will recruit Tregs to the site of action and enable/enforce their activities. The APC will also be enabled to directly recruit regenerative cells to the site(s) in need of repair once the inflammatory environment has been quelled. These vectored movements will be mediated by Proxykines - genetically modified chemotactic cytokines (chemokines) that are paired with unique and specific orthogonal receptors. All of the above modifications will create an encapsulated, functional immune system that operates autonomously of the host immune system into which it is introduced.