| Autor: |
Sterman, Daniel H, Molnar-Kimber, Katherine, Iyengar, Tara, Chang, Michael, Lanuti, Michael, Amin, Kunjlata M, Pierce, Brandon K, Kang, Eugene, Treat, Joseph, Recio, Adri, Litzky, Leslie, Wilson, James M, Kaiser, Larry R, Albelda, Steven M |
| Předmět: |
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| Zdroj: |
Cancer Gene Therapy; Dec2000, Vol. 7 Issue 12, p1511, 8p |
| Abstrakt: |
One of the primary limitations of adenoviral (Ad)-mediated gene therapy is the generation of anti-Ad inflammatory responses that can induce clinical toxicity and impair gene transfer efficacy. The effects of immunosuppression on these inflammatory responses, transgene expression, and toxicity have not yet been systematically examined in humans undergoing Ad-based gene therapy trials. We therefore conducted a pilot study investigating the use of systemic corticosteroids to mitigate antivector immune responses. In a previous phase I clinical trial, we demonstrated that Ad-mediated intrapleural delivery of the herpes simplex virus thymidine kinase gene (HSVtk) to patients with mesothelioma resulted in significant, but relatively superficial, HSVtk gene transfer and marked antiAd humoral and cellular immune responses. When a similar group of patients was treated with Ad.HSVtk and a brief course of corticosteroids, decreased clinical inflammatory responses were seen, but there was no demonstrable inhibition of anti-Ad antibody production or Ad-induced peripheral blood mononuclear cell activation. Corticosteroid administration also had no apparent effect on the presence of intratumoral gene transfer. Although limited by the small numbers of patients studied, our data suggest that systemic administration of steroids in the context of Ad-based gene delivery may limit acute clinical toxicity, but may not inhibit cellular and humoral responses to Ad vectors. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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