title: A phase I trial of Ad.hIFN-beta gene therapy for glioma.
abstract: Interferon-beta (IFN-beta) is a pleiotropic cytokine with antitumoral activity. In an effort to improve the therapeutic index of IFN-beta by providing local, sustained delivery of IFN-beta to gliomas, the safety and biological activity of a human IFN-beta (hIFN-beta)-expressing adenovirus vector (Ad.hIFN-beta) was evaluated in patients with malignant glioma by stereotactic injection, followed 4-8 days later by surgical removal of tumor with additional injections of Ad.hIFN-beta into the tumor bed. Eleven patients received Ad.hIFN-beta in cohorts of 2 x 10(10), 6 x 10(10), or 2 x 10(11) vector particles (vp). The most common adverse events were considered by the investigator as being unrelated to treatment. One patient, who was enrolled in the cohort with the highest dose levels, experienced dose-limiting, treatment-related Grade 4 confusion following the post-operative injection. Ad.hIFN-beta DNA was detected within the tumor, blood, and nasal swabs in a dose-dependent fashion and hIFN-beta protein was detectable within the tumor. At the highest doses tested, a reproducible increase in tumor cell apoptosis in post-treatment versus pre-treatment biopsies with associated tumor necrosis was observed. Direct Ad.hIFN-beta injection into the tumor and the surrounding normal brain areas after surgical removal was feasible and associated with apoptosis induction.
authors.affiliation: Department of Neurosurgery, Dardinger Neuro-oncology Center, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio 43210-1240, USA. EA.Chiocca@osumc.edu
authors.forename: E Antonio
authors.initials: EA
authors.lastname: Chiocca
authors.forename: Katie M
authors.initials: KM
authors.lastname: Smith
authors.forename: Byron
authors.initials: B
authors.lastname: McKinney
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Palmer
authors.forename: Steven
authors.initials: S
authors.lastname: Rosenfeld
authors.forename: Kevin
authors.initials: K
authors.lastname: Lillehei
authors.forename: Allan
authors.initials: A
authors.lastname: Hamilton
authors.forename: Betty K
authors.initials: BK
authors.lastname: DeMasters
authors.forename: Kevin
authors.initials: K
authors.lastname: Judy
authors.forename: David
authors.initials: D
authors.lastname: Kirn
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000097:blood / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D015850:Interleukin-6; D016753:Interleukin-10; D016899:Interferon-beta