Antigen-specific tolerance strategies for the prevention and treatment of autoimmune disease

Key Points The development of antigen-specific therapies for the treatment of autoimmune disease will allow for the tolerization of autoreactive immune cells, while maintaining the ability of the host's immune system to recognize foreign antigen. Human trials are often designed to parallel experiences in animal models of the disease; however, the transition between outcomes in experimental animal models and human trials is often not straight forward. There are currently four different protocols employed for inducing peptide-specific immune tolerance — soluble-peptide-induced and DNA-vaccination-induced tolerance, mucosal (oral or nasal)-induced tolerance, coupled-cell-induced tolerance, and altered peptide ligand (APL)-induced tolerance — that work by various different mechanisms. Three of the protocols for the induction of antigen-specific tolerance have been tested in initial clinical trails: soluble-peptide-induced and DNA-vaccination-induced tolerance, mucosal (oral or nasal)-induced tolerance and APL-induced tolerance. A Phase I and II clinical trial has been awarded provisional support by the Immune Tolerance Network pending US Food and Drug Administration (FDA) approval, to test the safety and efficacy of antigen-coupled-cell-induced tolerance in early relapsing–remitting MS. The clinical efficacy of antigen- or peptide-specific immunotherapies for the treatment of pre-existing autoimmune disease is still uncertain. Therapeutic strategies that induce antigen-specific immune tolerance without suppressing the ability of the immune system to respond to infectious agents are needed for the treatment of autoimmune diseases. But how might these antigen-specific therapies induce tolerance and are they safe for use in the clinic? The development of safe and effective antigen-specific therapies is needed to treat patients with autoimmune diseases. These therapies must allow for the specific tolerization of self-reactive immune cells without altering host immunity to infectious insults. Experimental models and clinical trials for the treatment of autoimmune disease have identified putative mechanisms by which antigen-specific therapies induce tolerance. Although advances have been made in the development of efficient antigen-specific therapies, translating these therapies from bench to bedside has remained difficult. Here, we discuss the recent advances in our understanding of antigen-specific therapies for the treatment of autoimmune diseases.