Long-term hepatic adenovirus-mediated gene expression in mice following CTLA4Ig administration.
Recombinant adenovirus vectors are efficient at transferring genes into somatic tissues but are limited for use in clinical gene therapy by immunologic factors that result in the rapid loss of gene expression and inhibit secondary gene transfer. This study demonstrates that systemic coadministration of recombinant adenovirus with soluble CTLA4Ig, which is known to block co-stimulatory signals between T cells and antigen presenting cells, leads to persistent adenoviral gene expression in mice without long-term immunosuppression. This form of immunotherapy greatly enhances the likelihood that recombinant adenovirus vectors will be useful for human gene therapy.
Kay
M A
MA
Department of Medicine, University of Washington, Seattle 98195, USA.
Holterman
A X
AX
Meuse
L
L
Gown
A
A
Ochs
H D
HD
Linsley
P S
PS
Wilson
C B
CB
D000069594:Abatacept; D000256:Adenoviridae; D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000096:biosynthesis; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007074:Immunoglobulin G; D000515:alpha 1-Antitrypsin; D000069594:Abatacept