title: Targeting the alternatively spliced soluble isoform of CTLA-4: prospects for immunotherapy?
abstract: CTLA-4 is an inhibitory protein that contributes to immune homeostasis and tolerance, a role that has led to its exploitation as a therapeutic in several clinical settings including cancer and autoimmune disease. Development of CTLA-4 therapies focused largely on the full-length receptor isoform but other CTLA-4 isoforms are also expressed, including a secretable form of CTLA-4 (soluble CTLA-4 [sCTLA-4]). The contribution of sCTLA-4 to immune regulation has been less well studied, primarily because it was identified some years after the original description of CTLA-4. Here, we examine how sCTLA-4 might contribute to immune regulation and ask whether it might be a biomarker to inform current CTLA-4 therapies or represent a novel CTLA-4 target for future therapeutics.
authors.affiliation: Section of Immunology & Infection, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Ward
authors.forename: Lekh N
authors.initials: LN
authors.lastname: Dahal
authors.forename: Rahul C
authors.initials: RC
authors.lastname: Khanolkar
authors.forename: Sucharita P
authors.initials: SP
authors.lastname: Shankar
authors.forename: Robert N
authors.initials: RN
authors.lastname: Barker
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D060908:CTLA-4 Antigen / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D020033:Protein Isoforms / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; D020033:Protein Isoforms
keywords: CTLA-4 isoforms; CTLA4-Ig; T-cell costimulation; ipilimumab; melanoma; rheumatoid arthritis; sCTLA-4; tremelimumab