The phase 1b trial was conducted at the Ohio State University Comprehensive Cancer Centre - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) and at Methodist at Hospital in Houston, TX.
The novel treatment 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 removing brain tumors such as glioblastoma multiforme, the most common and dangerous form of brain cancer.
The findings, published online in the Journal of Clinical Oncology, suggest that the therapy might also stimulate an immune response against the tumour.
"This is the first time that a gene therapy approach was combined with radiation in patients with a newly diagnosed glioblastoma," says first author Dr. E. Antonio Chiocca, professor and chair of neurological surgery and co-director of Ohio State's Dardinger Centre for Neuro-oncology and Neurosciences.
"There had been a concern that combining these two treatments could be too toxic for patients, but this was not the case. We do not know yet if this will improve survival, but these findings are encouraging," he says.
Glioblastomas occur in about 18 500 Americans annually and kill nearly 13 000 of them yearly. 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 where they can give rise to a recurrent tumour. This study examines an immunogene therapy approach that is designed to kill these undetected cancer cells and prevent recurrence.
This clinical trial involved 10 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. The procedure works as follows:
In addition to improved overall survival, studies revealed a significant rise in the number of T lymphocytes in the tumors. This suggests that the gene therapy stimulated an immune response against the tumour, producing an "immunogene therapy" effect.
Cancer immunogene therapy refers to genetically manipulating cancer cells to stimulate an immune response against a tumour. (Note: This differs from "immunotherapy," which attempts to stimulate the immune system directly against tumour cells.)
"If the results of another recently completed phase 2 efficacy trial are also encouraging, the next step will be to compare this therapy head-to-head with the current standard of care," Chiocca says.
Funding from the National Cancer Institute and Advantagene, Inc. (Woburn, MA), supported this research.
Other researchers involved in this study were Susan D. Bell, Balveen Kaur, Jayson Hardcastle, Robert Cavaliere, John McGregor, Simon Lo, Abhik Ray Chaudhuri, Arnab Chakarvarti, John Grecula, and Herbert Newton of the Dardinger Neuro-oncology Centre and Ohio State University; Kimbra S. Harris, Robert G. Grossman, Todd W. Trask, David S. Baskin, and Pamela Z. New of Methodist Hospital Neurological Institute; and Laura K. Aguilar, Carissa M. Monterroso, Andrea G. Manzanera, and Estuardo Aguilar-Cordova of Advantagene, Inc.
