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Treg‐based immunotherapy of non‐infectious uveitis ( NIU )
Author(s) -
Asnagli H.,
Jacquin M.,
Belmonte N.,
GertnerDardenne J.,
Hubert M.F.,
Sales A.,
Foussat A.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0385
Subject(s) - immunology , in vivo , inflammation , medicine , granzyme b , immunotherapy , biology , t cell , immune system , microbiology and biotechnology
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.