LX211 (voclosporin) suppresses experimental uveitis and inhibits human T cells.
OBJECTIVE
To test the therapeutic effectiveness of voclosporin against experimental autoimmune uveoretinitis (EAU) in rats and to evaluate its effect on human T cells.


METHODS
EAU was induced by immunization with a uveitogenic protein. Voclosporin administration, by subcutaneous injection, began on day (d) 0 or d7 after immunization. Treatment effectiveness was evaluated in vivo using clinical EAU scoring (d7-d13) and histopathologic evaluation of enucleated eyes after experimental termination. Rodent lymphocytes were harvested from lymph nodes on d14 for antigen-specific proliferation assays. The effect of voclosporin on human T-cell proliferation and cytokine secretion was examined in vitro.


RESULTS
Voclosporin prevented EAU development in rats receiving medium and high preventive doses, whereas high-dose voclosporin administration effectively treated EAU. Lymphocytes from animals treated with voclosporin had decreased antigen-specific proliferation in vitro compared with lymphocytes from untreated animals. No evidence of abnormal ocular histopathology was found in the eyes from animals that received high doses of therapeutic voclosporin. Using human T cells, voclosporin inhibited human T-cell proliferation up to 100-fold. Furthermore, voclosporin treatment of human T cells significantly reduced pan T-cell effector responses.


CONCLUSIONS
Voclosporin effectively suppressed uveoretinitis in an animal model that imitates the human inflammatory ocular disease by inhibiting lymphocyte proliferation. In addition, voclosporin effectively inhibited human T-cell proliferation and function in vitro. The authors report the first evidence supporting the application of voclosporin to treat intraocular inflammation.
Cunningham
Matthew A
MA
National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA.
Austin
Bobbie Ann
BA
Li
Zhuqing
Z
Liu
Baoying
B
Yeh
Steven
S
Chan
Chi-Chao
CC
Anglade
Eddy
E
Velagaleti
Poonam
P
Nussenblatt
Robert B
RB
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D016572:Cyclosporine; D016207:Cytokines; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C484071:voclosporin