Antigen-specific tolerance to self-antigens in protein replacement therapy, gene therapy and autoimmunity. (December 2019)

• Record Type: Journal Article
• Authors: Steinman, Lawrence; Ho, Peggy P; Robinson, William H; Utz, Paul J; Villoslada, Pablo
• Is Part Of: Current opinion in immunology. Volume 61(2019)
• Page Start: 46
• Page End: 53
• Publication Date: 2019-12
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2019.07.011
• Languages: English
• ISSNs: 0952-7915

Abstract

Highlights: Current therapies for autoimmunity halt natural immune surveillance. High doses of Factor VIII administered in hemophilia A induce tolerance. Gene replacement therapy can be enhanced by antigen-specific tolerization. Antigen-specific tolerization is a targeted approach to treating clinical disease. Abstract : Trials of antigen-specific tolerance have been undertaken in the clinic for over fifty years and the results of these antigen-specific clinical trials are described in this review. Antigen-specific tolerization of the immune system in protein replacement therapy for hemophilia A is an accepted treatment. Clinical trials are ongoing for autoimmune conditions such as type 1 diabetes, multiple sclerosis, neuromyelitis optica, and rheumatoid arthritis with various antigen-specific strategies. Trials for tolerization in celiac disease aim for antigen specific tolerance to gluten, an environmental trigger, which may then halt the progression to autoimmunity targeting a self-antigen, tissue transglutaminase. Although many promising approaches have been demonstrated in pre-clinical models, this review will focus primarily on clinical trials of antigen-specific tolerance that have been taken to the clinic and with initial results reported in the peer reviewed literature. A separate article on approaches with CAR-T cells appears in this volume.