Use of MRJ in the follow-up of IL-4 mediated gene therapy of rat experimental gliomas

Glioblastomas (GBL) constitute a relevant target for novel strategies of gene therapy. We previously suggested that gene transfer of interleukin 4 (IL-4) can complement therapies based on retroviral tranfer of the 'suicide' gene Herpes Simplex Virus- thymidine kinase (HSV-tk) and administration of ganciclovir (Benedetti et al, in press). To further define the efficacy of IL-4 alone or associated with HSV-tk-based therapies, we used MRJ for the follow-up of untreated C6 GBL grafted into rat brain by stereotactic techniques used as a control groups (n=9), or, treated with retroviral producer cells (RFC) expressing IL-4 (group A, n=14) or with IL-4 and HSV-tk RPC (group B, n=8 rats). In the 9 controls (survival after injection 23.5±1.9 days), mass effect, signal abnormalities and uptake of gadolinium DTPA were evident, six of 14 animals in group A (43%) and 4/8 in group B (50%) died during the first two months while 8/14 and 4/8, respectively, survived for at least 4 months. MRI demonstrated the presence of a large GBLin all cases at the first exsamination and the regression of the tumor in treated long-term survivors. These findings demonstrate the relevance of MRI for the follow-up of gene therapy of gliomas and, in agreement with survival data obtained in a larger group of animals not investigated by MRI, suggest that gene transfer of IL-4, by itself, can be very effective in the treatment of these malignancies.