Immunotherapeutic strategies in autoimmune uveitis.
Autoimmune uveitis is an organ-specific disorder characterized by irreversible lesions to the eye that predominantly affect people in their most productive years and is among the leading causes of visual deficit and blindness. Currently available therapies are effective in the treatment of a wide spectrum of uveitis, but are often associated with severe side effects. Here, we review ongoing research with promising immunomodulatory therapeutic strategies, describing their specific features, interactions and the responses triggered by the targeted immune molecules that aim to minimize clinical complications and the likelihood of disease relapse. We first review the main features of the disease, diagnostic tools, and traditional forms of therapy, as well as the animal models predominantly used to understand the pathogenesis and test the novel intervention approaches aiming to control the acute immune and inflammatory responses and to dampen chronic responses. Both exploratory research and clinical trials have targeted either the blockade of effector pathways or of their companion co-stimulatory molecules. Examples of targets are T cell receptors (CD3), their co-stimulatory receptors (CD28, CTLA-4) and corresponding ligands (B7-1 and B7-2, also known as CD80 and CD86), and cytokines like IL-2 and their receptors. Here, we summarize the available evidence on effectiveness of these treatments in human and experimental uveitis and highlight a novel CD28 antagonist monovalent Fab' antibody, FR104, which has shown preclinical efficacy suppressing effector T cells while enhancing regulatory T cell function and immune tolerance in a humanized graft-versus-host disease (GVHD) mice model and is currently being tested in a mouse autoimmune uveitis model with encouraging results.
Hospital Israelita Albert Einstein, Av. Albert Einstein 627-701, 2-SS Bloco A, 05651-901 São Paulo, Brazil.
Pedro Henrique
PH
Papotto
Hospital Israelita Albert Einstein, Av. Albert Einstein 627-701, 2-SS Bloco A, 05651-901 São Paulo, Brazil.
Eliana Blini
EB
Marengo
Hospital Israelita Albert Einstein, Av. Albert Einstein 627-701, 2-SS Bloco A, 05651-901 São Paulo, Brazil.
Luiz Roberto
LR
Sardinha
Hospital Israelita Albert Einstein, Av. Albert Einstein 627-701, 2-SS Bloco A, 05651-901 São Paulo, Brazil; Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (iii-INCT), Brazil.
Anna Carla
AC
Goldberg
Hospital Israelita Albert Einstein, Av. Albert Einstein 627-701, 2-SS Bloco A, 05651-901 São Paulo, Brazil; Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (iii-INCT), Brazil. Electronic address: lvrizzo@einstein.br.
Luiz Vicente
LV
Rizzo
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D004731:Endotoxins / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000628:therapy
D004731:Endotoxins
Autoimmune uveitis; CD28 antagonists; Costimulation blockade; Experimental autoimmune uveitis; Immune modulation