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Titolo:
A pilot study of systemic corticosteroid administration in conjunction with intrapleural adenoviral vector administration in patients with malignant pleural mesothelioma
Autore:
Sterman, DH; Molnar-Kimber, K; Iyengar, T; Chang, M; Lanuti, M; Amin, KM; Pierce, BK; Kang, E; Treat, J; Recio, A; Litzky, L; Wilson, JM; Kaiser, LR; Albelda, SM;
Indirizzi:
Univ Penn, Med Ctr, Div Pulm & Crit Care Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Care Med, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Dept Surg, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 tol Oncol, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 pt Pathol, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 ular Engn, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Inst Human Gene Therapy, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 e Therapy, Philadelphia, PA 19104 USA
Titolo Testata:
CANCER GENE THERAPY
fascicolo: 12, volume: 7, anno: 2000,
pagine: 1511 - 1518
SICI:
0929-1903(200012)7:12<1511:APSOSC>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEDIATED GENE-TRANSFER; CELLULAR IMMUNE-RESPONSES; I CLINICAL-TRIAL; HUMAN CFTR CDNA; RECOMBINANT ADENOVIRUS; TRANSGENE EXPRESSION; NONHUMAN-PRIMATES; PHASE-I; THYMIDINE KINASE; CYSTIC-FIBROSIS;
Keywords:
mesothelioma; adenovirus; intrapleural; immunosuppression; corticosteroids; thymidine kinase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Sterman, DH Div Pulm Allergy & Crit Care Med, 833 W Gates Bldg,3400 SpruceSt, Philadelphia, PA 19104 USA Div Pulm Allergy & Crit Care Med 833 W Gates Bldg,3400 Spruce St Philadelphia PA USA 19104
Citazione:
D.H. Sterman et al., "A pilot study of systemic corticosteroid administration in conjunction with intrapleural adenoviral vector administration in patients with malignant pleural mesothelioma", CANC GENE T, 7(12), 2000, pp. 1511-1518

Abstract

One of the primary limitations of adenoviral (Ad)-mediatcd gene therapy isthe generation of anti-Ad inflammatory responses that fan 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 anti-Ad humoral and cellular immune responses.(1,2) 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.

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Documento generato il 29/09/20 alle ore 21:19:35