Bench to bedside of CTLA-4: a novel immuno-therapeutic agent for inflammatory disorders.
Co-stimulatory molecules are antigen-independent generators of secondary signals which aid in maintaining the homeostasis of the immune system. CTLA-4 is one among extensively studied co-stimulatory molecules which down-regulate immune response. The attributes of immunosuppressive qualities and capacity to induce tolerance have made its recognition as a potential immuno-therapeutic agent for autoimmune mediated inflammatory disorders. In 2007, European Medical Drug Agency (EMEA) has approved administration of CTLA-4Ig (commercial name: Orencia; generic name: Abatacept), as a mean for co-stimulation blockade, for treating patients with rheumatoid arthritis. This review is focused on working mechanism of CTLA-4 from its recognition (bench) to its usage as a potential therapeutic agent (bedside) for several inflammatory diseases. The efficacious aspects of chimeric CTLA-4 in phase I, II and III clinical trials for rheumatoid arthritis, psoriasis, multiple sclerosis are concisely described. This article highlights recent patents and the future usage of co-stimulatory molecules as a therapeutic agent providing a promising immuno-modulatory approach in regulating inflammation.
Sakthivel
Priya
P
Rheumatology Unit, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden. priya.sakthivel@ki.se
D000069594:Abatacept; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy; D060908:CTLA-4 Antigen; D002986:Clinical Trials as Topic; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy*; D011110:Polymorphism, Genetic; D011565:Psoriasis / Q000276:immunology / Q000628:therapy*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept