Cellular immunotherapy of chronic inflammation and autoimmunity using autologous antigen-specific T regulatory (Treg) cells

Among the most innovative immunotherapies, autologous cellular immunotherapy aims at treating patients with their own immune cells that, before reinjection, have been educated ex vivo to fight disease. Antigen-specific regulatory T cells (Ag-Treg) are recognized as a promising tool for therapeutic intervention in patients with chronic inflammation and autoimmunity. Ovasave ® is an autologous ovalbumin-specific Treg (Ova-Treg) product that is in development for the treatment of severe Crohn's disease patients refractory to available treatments. Ovasave ® has shown a good tolerability and dose-related efficacy in a first-in-man open-labeled phase I/IIa study in refractory Crohn's disease patients. In this study, a 75% response rate and a 38% remission rate on the CDAI (Crohn's Disease Activity Index) were observed at the best dose. In addition, clinical response was correlated with a decrease in vitro proliferation of patient's white blood cells in response to ovalbumin, indicating that decreased proliferation to Ag-Treg specific antigen could be used as a biomarker of clinical response. A randomized controlled phase IIb clinical study with Ovasave will start mid-2014 to confirm the efficacy and tolerability of Ovasave ® in refractory's Crohn's disease patients. Ag-Treg manufacturing has been developed to be highly cost-effective and logistically simple: multiple years of treatment doses are manufactured by one processing from one blood sample. Ovasave ® is the lead product from TxCell's ASTrIA platform Ag-Treg products. From this platform, Col-Treg, an autologous collagen-II specific based product is in the final preclinical stage of development for the treatment of patients with autoimmune uveitis, an orphan chronic inflammatory condition of the eye, with a phase I/IIa clinical study planned for 2015. With Ovasave ® and Col-Treg as novel, personalized cellular immunotherapies for chronic autoimmune inflammatory diseases, Ag-Tregs represent a new therapeutic opportunity for patients who today have few or no treatment options.