Cyclosporin A does not affect adenoviral-mediated transgene expression of interleukin-2.
The adenoviral vector demonstrates efficient gene transfer and high transient gene expression making it an attractive vehicle for human gene therapy trials. Unfortunately, the virus stimulates a potent inflammatory immune response that limits transgene expression and makes repeat viral dosing ineffective. Transient immunosuppression has emerged as one technique to prolong adenoviral-mediated transgene expression and enable readministration of the viral vector. Cyclosporin A (CsA) causes immunosuppression by blocking the promotor/enhancer region of the gene for interleukin-2 (IL-2). The affect of CsA on transgene IL-2 expression was examined. Viral-mediated gene transfer was optimized in a human cell line using a type five adenoviral vector (Ad5) containing the gene for human IL-2 or bacterial beta-galactosidase (lac-Z) driven by a cytomegalovirus (CMV) promoter. CsA at various concentrations had no affect on IL-2 or lac-Z transgene expression. The immunosuppressive drug CsA is known to block native IL-2 transcription but has no affect on the adenoviral-mediated IL-2 or lac-Z transgene.
Wilkinson
N W
NW
General Surgery Service, Eisenhower Army Medical Center, Fort Gordon, GA 30905, USA. Neal.Wilkinson@se.amedd.army.mil
Euhus
D M
DM
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D001943:Breast Neoplasms; D003524:Cyclosporins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000032:analysis* / Q000276:immunology; D012016:Reference Values; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D003524:Cyclosporins; D007376:Interleukin-2; C050026:cyclosporin D