CTLA4Ig gene transfer prolongs survival and induces donor-specific tolerance in a rat renal allograft

Susanna Tomasoni, Nadia Azzollini, Federica Casiraghi, Maurizio C. Capogrossi, Giuseppe Remuzzi, Ariela Benigni

Research output: Contribution to journalArticle

Abstract

Organ transplantation requires lifelong antirejection therapy, which carries the risk of infection and cancer. A revolutionary approach is to transduce the organ graft with immunomodulatory genes to render them tolerated with no need of systemic immunosuppression. Prolonged allograft survival was achieved by adenovirus-mediated transduction of the cold- preserved kidney with sequences encoding CTLA4Ig, a recombinant fusion protein that blocks T cell activation. Organ expression of the transgene was achieved associated with mild infiltration of mononuclear cells in the transfected kidney. Mixed lymphocyte reaction as well as the production of both Th1 and Th2 cytokines were reduced. Thus, the gene transfer technique to prolong graft survival is indeed effective and safe and can induce donor- specific unresponsiveness. Pending appropriate large animal testing, ex vivo genetic manipulation of the organ before surgery may hopefully represent a major step forward in human transplant medicine.

Original languageEnglish
Pages (from-to)747-752
Number of pages6
JournalJournal of the American Society of Nephrology
Volume11
Issue number4
Publication statusPublished - Apr 2000

ASJC Scopus subject areas

  • Nephrology

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