Treg-based immunotherapy of non-infectious uveitis (NIU)
Abstract
Purpose
Col-Treg is a T-cell immunotherapy composed of autologous type-1 regulatory T (Treg) cells specific for collagen-II. Col-Treg are tested in NIU mice as collagen-II is present in the eye, allowing the triggering of their activity in situ. NIU is one of the most common cause of blindness in the developed world.
Methods
Col-Treg cells are produced from blood of healthy volunteers or splenocytes of mice transgenic for collagen-II-specific TCR. Cells are characterized for marker expression using FACS and for in-vitro immuno-modulatory function. NIU model was induced by IRPB immunization. In-vivo efficacy was evaluated with ophthalmoscopy histology, pro-inflammatory cytokines analysis. In-vivo tracking was performed using a Col-Treg TCR specific quantitative PCR.
Results
Col-Treg secrete IL10, IL13 and express GITR, CD39 and Granzyme B, molecules involved in the control of inflammation. Col-Treg hydrolyse ATP, kill myeloid cells and inhibit T effector cell IL17 and IFNg secretion. Intravenous administration of Col-Treg inhibited ocular inflammation in NUI mice with reduction of cellular infiltrates, IL1β, IL6, TNFα. In-vivo-tracking demonstrated a tropism of Col-Treg for inflammatory eyes. In-vivo GLP toxicity study in healthy mice did not revealed Col-Treg related adverse events. Characterization of human Col-Treg GMP batches demonstrated comparability with mouse Col-Treg for marker expression and in vitro function.
Conclusions
These data demonstrate the safety and efficacy of Col-Treg administration for the treatment of NIU in mice, suggesting that Col-Treg could be used as a therapeutic tool for patients with non-infectious uveitis refractory to approved medications.
