A phase I clinical trial of a genetically modified and imageable oncolytic vaccinia virus GL-ONC1 with clinical green fluorescent protein (GFP) imaging

Autor:	N. Tunariu, David Mansfield, T. A. Yap, M. Puglisi, Kevin J. Harrington, K. A. Denholm, J.S. de Bono, J. V. Pedersen, Eleni M. Karapanagiotou, A. Biondo, Salem Sassi
Rok vydání:	2011
Předmět:	Cancer Research Reporter gene biology business.industry Virology Molecular biology Oncolytic virus Green fluorescent protein Genetically modified organism Fusion gene chemistry.chemical_compound Oncology chemistry Thymidine kinase biology.protein Medicine Vaccinia business Neutralizing antibody
Zdroj:	Journal of Clinical Oncology. 29:2577-2577
ISSN:	1527-7755 0732-183X
DOI:	10.1200/jco.2011.29.15_suppl.2577
Popis:	2577 Background: GL-ONC1 is a genetically engineered vaccinia virus attenuated by insertion of the ruc-gfp (Renilla luciferase and Aequorea green fluorescent protein fusion gene), beta-galactosidase (lacZ) and beta-glucuronidase (gusA) reporter genes into the F14.5L, J2R (thymidine kinase) and A56R (hemagglutinin) loci, respectively. A Phase I trial of intravenous GL-ONC1 was pursued to evaluate safety, tolerability, tumour delivery, neutralizing antibody development and anti tumour activity. Methods: GL-ONC1 was to be administered at escalating doses (1×105, 1×106, 1×107, 1×108, 1×109, 3×109 plaque-forming units (pfu) on day 1 only; 1.667×107 and 1.667×108 pfu on day 1-3; 1×109 pfu on day 1-5) using a 3+3 dose escalation design and a q28 days schedule. GFP imaging was performed at baseline and after each cycle on superficial and mucosal lesions. Results: To date, 21 patients (males 15, median age 57 years) have been treated without dose limiting toxicities. Adverse events reported were generally mild (gr...
Databáze:	OpenAIRE
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