T cell immunomodulation--the Holy Grail of therapeutic tolerance.
The concept and practice of therapeutic tolerance has successfully been applied to animal models of autoimmunity and transplantation for more than 2 decades. Finally, there are encouraging signs of its translation to clinical practice. Short courses of anti-CD3 monoclonal antibody therapy have provided lasting benefits in recent-onset type 1 diabetes in association with evidence for the induction of immunoregulatory mechanisms. Co-stimulation blockade with abatacept (CTLA4-Ig) will soon be licensed for the treatment of rheumatoid arthritis - over the past year phase III studies have demonstrated impressive improvement in subjective and objective signs of the disease. T cell depletion is in development for several conditions, again with recent studies demonstrating evidence of immune regulation in some instances. More specific antigen-directed peptide therapies have also been applied to atopic asthma, type 1 diabetes, and adult and juvenile arthritis. The tragic sequelae of the phase I trial of TGN1412 at Northwick Park demonstrated the delicate, but unpredictable, therapeutic ratio of some T-cell-directed treatments and, in the UK, have led to new guidelines for early-phase clinical trials of immune-directed therapies.
Isaacs
John D
JD
Wilson Horne Immunotherapy Centre and Musculoskeletal Research Group, Institute of Cellular Medicine, Catherine Cookson Building, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom. j.d.isaacs@ncl.ac.uk
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000941:Antigens / Q000187:drug effects / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy*; D017252:CD3 Complex / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D007108:Immune Tolerance; D016377:Organ Transplantation; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014181:Transplantation Immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D017252:CD3 Complex