Encouraging Combination

Immunogene Therapy Plus Standard Treatment Found Safe

E Antonio ChioccaResearchers at Ohio State have learned through a clinical trial that a type of gene therapy is safe for treating a deadly brain cancer, even when combined with radiation therapy.

The phase I-B trial, conducted at the OSUCCC – James and at Methodist Hospital in Houston, involved a novel treatment that uses an adenovirus vector called AdV-tk. The vector is taken up by cancer cells, where it activates a drug that kills the cells. The vector is applied in the operating room after removal of tumors such as glioblastoma multiforme, the most common and dangerous form of brain cancer.

The findings suggest that this therapy might also stimulate an immune response against the tumor.

“This is the first time a gene therapy approach was combined with radiation in patients with a newly diagnosed glioblastoma,” says first author E. Antonio Chiocca, MD, PhD, professor and chair of Neurological Surgery at Ohio State. “There had been a concern that combining these two treatments could be too toxic, but this was not the case. We don’t know yet if this will improve survival, but these findings are encouraging.”

Glioblastomas annually occur in about 18,500 Americans and kill nearly 13,000. Glioblastoma multiforme is the most common and lethal form of the malignancy, with an average survival of 15 months after diagnosis.

The tumors often recur because cancer cells typically migrate into adjacent brain tissue. This study, which involved 10 patients with glioblastoma multiforme and two with anaplastic astrocytoma, examined an immunogene therapy approach that is designed to kill these undetected cancer cells and prevent recurrence.

In addition to improved overall survival, the study revealed a significant rise in T lymphocytes in the tumors, suggesting that the gene therapy stimulated an immune response against the tumor, producing an “immunogene therapy” effect.

Published in the Journal of Clinical Oncology.

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