A gene therapy or purified CTLA4IgG treatment of experimental allergic encephalomyelitis.
We examined whether multiple intraperitoneal injection of a soluble form of a chimeric protein consisting of an extracellular portion of cytotoxic T lymphocyte-associated protein 4 and an Fc portion of human IgG1(CTLA4IgG) at the initiation phase could successfully control the subsequent development of experimental allergic encephalomyelitis (EAE). We demonstrated that CTLA4IgG treatment could delay the onset and reduce the severity of EAE in early phase of disease development. More importantly, CTLA4IgG treatment significantly reduced the incidence of EAE. This was in good agreement to that spleen cells obtained from CTLA4IgG-treated animals responded poorly to myelin basic protein (MBP) in vitro as compared to those from human IgG-treated animals. However, the CTLA4IgG-treated mice eventually developed EAE and after all, incidence of EAE was not significantly different from that in control group. We then tested whether a gene therapy using adenovirus vector containing CTLA4IgG (Adex1CACTLA4IgG) could inhibit the development of EAE. We demonstrated that incidence and severity of EAE were significantly inhibited by a single injection of intravenous Adex1CACTLA4IgG up to 8 months. Thus, this study demonstrated the efficacy of a single dose of adenovirus-mediated gene therapy in controlling EAE as compared to repeated injection of purified CTLA4IgG proteins.
Kawaguchi
Y
Y
Section of Immunopathogenesis, Hokkaido University, Sapporo, Japan.
D000069594:Abatacept; D000256:Adenoviridae; D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D060908:CTLA-4 Antigen; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000276:immunology; D007275:Injections, Intravenous; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D000069594:Abatacept