Treatment of autoimmune disease by adoptive cellular gene therapy.
Autoimmune disorders represent inappropriate immune responses directed at self-tissue. Antigen-specific CD4+ T cells and antigen-presenting dendritic cells (DCs) are important mediators in the pathogenesis of auto-immune disease and thus are ideal candidates for adoptive cellular gene therapy, an ex vivo approach to therapeutic gene transfer. Using retrovirally transduced cells and luciferase bioluminescence, we have demonstrated that primary T cells, T cell hybridomas, and DCs rapidly and preferentially home to the sites of inflammation in animal models of multiple sclerosis, arthritis, and diabetes. These cells, transduced with retroviral vectors to drive expression of various "regulatory proteins" such as IL-4, IL-10, IL-12p40, and anti-TNF scFv, deliver these immunoregulatory proteins to the inflamed lesions, providing therapy for experimental autoimmune encephalitis (EAE), collagen-induced arthritis (CIA), and nonobese diabetic mice (NOD).
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California 94305, USA.
Ingo H
IH
Tarner
Anthony J
AJ
Slavin
Jacqueline
J
McBride
Alenka
A
Levicnik
Richard
R
Smith
Garry P
GP
Nolan
Christopher H
CH
Contag
C Garrison
CG
Fathman
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy*; D003713:Dendritic Cells / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008163:Luminescent Measurements; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism