A Phase I Trial of Ad.hIFN-β Gene Therapy for Glioma.
Interferon-β (IFN-β) is a pleiotropic cytokine with antitumoral activity. In an effort to improve the therapeutic index of IFN-β by providing local, sustained delivery of IFN-β to gliomas, the safety and biological activity of a human IFN-β (hIFN-β)-expressing adenovirus vector (Ad.hIFN-β) 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-β into the tumor bed. Eleven patients received Ad.hIFN-β in cohorts of 2 × 1010, 6 × 1010, or 2 × 1011vector 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-β DNA was detected within the tumor, blood, and nasal swabs in a dose-dependent fashion and hIFN-β 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-β injection into the tumor and the surrounding normal brain areas after surgical removal was feasible and associated with apoptosis induction.
Department of Neurosurgery, Dardinger Neuro-oncology Center, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio, USA. Electronic address: EA.Chiocca@osumc.edu.
E Antonio
EA
Chiocca
Biogen Idec Inc., San Diego, California, USA.
Katie M
KM
Smith
Biogen Idec Inc., San Diego, California, USA.
Byron
B
McKinney
Division of Neuropathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Cheryl A
CA
Palmer
Department of Neurology, Division of Neuro-oncology, Columbia College of Physicians and Surgeons, New York, New York, USA.
Steven
S
Rosenfeld
Department of Neurosurgery, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Kevin
K
Lillehei
Department of Neurosurgery, University of Arizona Medical Center, Tucson, Arizona, USA.
Allan
A
Hamilton
Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Betty K
BK
DeMasters
Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kevin
K
Judy
Jennerex Biotherapeutics, San Francisco, California, USA.
David
D
Kirn