First, the patient undergoes computer-assisted resection of the recurrent tumor. At the time of surgery performed by the neurosurgeon, the adenovirus is introduced by direct stereotactic injection into the brain after tumor resection. The adenovirus vector has been engineered to be nonreplicating; therefore, the virus is severely limited in its ability to disseminate to areas outside the brain. Second, the patient will receive intravenous gancliclovir. Only tumoral cells are by the combination of the injected gene and the ganciclovir.
This phase I trial has the following specific aims:
To determine the clinical and histological toxicity of intratumor injection of a recombinant adenovirus expressing HSV-tk, followed by intravenous ganciclovir, in patients with recurrent glioma; and
To assess the response of malignant gliomas to this treatment by brain imaging with volumetric MRI scans.
There is currently little to offer patients with malignant brain tumors for whom standard treatment has failed. However, preclinical investigations have suggested that the transfer of a drug susceptibility gene into brain tumors may be possible and may result in the death of tumor cells.
Why is our protocol different from previous studies?
Previous gene therapy studies in glioma have used recombinant retroviruses as vectors. While still regarded as promising, this approach is inefficient in gene transfer. As a result, investigators at Mount Sinai have developed a replication defective adenovirus vector that is believed to be superior to that of prior gene therapy approaches. The adenovirus vector containing the herpes simplex thymidine kinase (HSV-tk) gene is injected into brain tumors to confer sensitivity to ganciclovir. In the presence of HSV-tk, ganciclovir is converted to a toxic metabolite that will kill cells containing the HSV-tk gene, i.e., tumor cells and neighboring cells.
