A phase I trial of Ad.hIFN-beta gene therapy for glioma.
Publication/Presentation Date
3-1-2008
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.
Volume
16
Issue
3
First Page
618
Last Page
626
ISSN
1525-0024
Published In/Presented At
Chiocca, E. A., Smith, K. M., McKinney, B., Palmer, C. A., Rosenfeld, S., Lillehei, K., Hamilton, A., DeMasters, B. K., Judy, K., & Kirn, D. (2008). A phase I trial of Ad.hIFN-beta gene therapy for glioma. Molecular therapy : the journal of the American Society of Gene Therapy, 16(3), 618–626. https://doi.org/10.1038/sj.mt.6300396
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
18180770
Department(s)
Administration and Leadership
Document Type
Article