Transgene expression after adenovirus-mediated retransfection of rat lungs is increased and prolonged by transplant immunosuppression

S. D. Cassivi, M. Liu, A. Boehler, A. K. Tanswell, A. S. Slutsky, S. Keshavjee, A. S. Wechsler, T. Rosengart, A. F. Carpentier, R. C. Robbins

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Objectives: Adenovirus-mediated gene therapy has been proposed as a potential treatment modality in lung transplantation. However, to date its utility has been limited by an inflammatory host immune response that not only limits the amount and duration of transgene expression but also obviates successful retransfection. Having previously shown that by administering triple-immunosuppression, as is routine in lung transplantation, we could increase and prolong transgene expression after initial transfection, we hypothesized that transgene expression after retransfection could also be increased and prolonged. Methods: Lewis rats underwent intratracheal adenovirus-mediated transfection with the β-galactosidase gene and were randomized to either the immunosuppression group, receiving daily cyclosporine (INN: ciclosporin), azathioprine, and methylprednisolone, or the control group (no immunosuppression). Five weeks later, rats were similarly retransfected and transgene expression and post-transfection inflammation were evaluated 1, 7, and 14 days after retransfection. Results: After retransfection, immunosuppressed rats had significantly higher levels of transgene expression (P < .001), whereas control rats had virtually no detectable levels. On histologic sections of the lungs, immunosuppressed rats had overall lesser grades of post-transfection inflammation. Conclusions: Transplant immunosuppression attenuates the severe immune response to gene transfer and permits increased, prolonged, and repeated transfection. Retransfection is now achievable in the immunosuppressed lung transplant setting to allow for chronic, repeated administrator of gene therapy.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume117
Issue number1
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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    Cassivi, S. D., Liu, M., Boehler, A., Tanswell, A. K., Slutsky, A. S., Keshavjee, S., Wechsler, A. S., Rosengart, T., Carpentier, A. F., & Robbins, R. C. (1999). Transgene expression after adenovirus-mediated retransfection of rat lungs is increased and prolonged by transplant immunosuppression. Journal of Thoracic and Cardiovascular Surgery, 117(1), 1-7. https://doi.org/10.1016/S0022-5223(99)70462-9