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.