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 Citations (Scopus)

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 - 1999
Externally publishedYes

Fingerprint

Transgenes
Adenoviridae
Immunosuppression
Transfection
Transplants
Lung
Lung Transplantation
Genetic Therapy
Galactosidases
Inflammation
Methylprednisolone
Azathioprine
Administrative Personnel
Cyclosporine
Genes
Control Groups
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

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

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 117, No. 1, 1999, p. 1-7.

Research output: Contribution to journalArticle

Cassivi, SD, Liu, M, Boehler, A, Tanswell, AK, Slutsky, AS, Keshavjee, S, Wechsler, AS, Rosengart, T, Carpentier, AF & Robbins, RC 1999, 'Transgene expression after adenovirus-mediated retransfection of rat lungs is increased and prolonged by transplant immunosuppression', Journal of Thoracic and Cardiovascular Surgery, vol. 117, no. 1, pp. 1-7. https://doi.org/10.1016/S0022-5223(99)70462-9
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. / Transgene expression after adenovirus-mediated retransfection of rat lungs is increased and prolonged by transplant immunosuppression. In: Journal of Thoracic and Cardiovascular Surgery. 1999 ; Vol. 117, No. 1. pp. 1-7.
@article{22decfe462354f7885c24b38e674466a,
title = "Transgene expression after adenovirus-mediated retransfection of rat lungs is increased and prolonged by transplant immunosuppression",
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.",
author = "Cassivi, {S. D.} and M. Liu and A. Boehler and Tanswell, {A. K.} and Slutsky, {A. S.} and S. Keshavjee and Wechsler, {A. S.} and T. Rosengart and Carpentier, {A. F.} and Robbins, {R. C.}",
year = "1999",
doi = "10.1016/S0022-5223(99)70462-9",
language = "English (US)",
volume = "117",
pages = "1--7",
journal = "Journal of Thoracic and Cardiovascular Surgery",
issn = "0022-5223",
publisher = "Mosby Inc.",
number = "1",

}

TY - JOUR

T1 - Transgene expression after adenovirus-mediated retransfection of rat lungs is increased and prolonged by transplant immunosuppression

AU - Cassivi, S. D.

AU - Liu, M.

AU - Boehler, A.

AU - Tanswell, A. K.

AU - Slutsky, A. S.

AU - Keshavjee, S.

AU - Wechsler, A. S.

AU - Rosengart, T.

AU - Carpentier, A. F.

AU - Robbins, R. C.

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032893898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032893898&partnerID=8YFLogxK

U2 - 10.1016/S0022-5223(99)70462-9

DO - 10.1016/S0022-5223(99)70462-9

M3 - Article

C2 - 9869751

AN - SCOPUS:0032893898

VL - 117

SP - 1

EP - 7

JO - Journal of Thoracic and Cardiovascular Surgery

JF - Journal of Thoracic and Cardiovascular Surgery

SN - 0022-5223

IS - 1

ER -