Regression of Intracerebral rat gliomas following in vivo retroviral gene transfer of interleukin-12 and HSVtk/GCV

BERENSTEIN, M.; CHEMES, L.; ADRIS, S.; DI PAOLO, N.; BRAVO, I.; CHERNAJOVSKY, Y.; PODHAJCER, O.

Denver, Colorado USA. May 31-June 4

Conferencia; The Third Annual Meeting of the American Society for Gene Therapy; 2000

American Society of Gene Therapy

Malignant primary and metastatic brain tumors are still as lethal as 20 years ago. Novel treatment strategies need to be developed in order to increase the limited efficiency of the current treatments. Others and we have shown that in vivo modification of glioma tumor cells with HSV-tk gene followed by GCV treatment (HSVtk/GCV) led to tumor rejection and the development of an anti-tumor immune memory. But, recent clinical data failed to support the experimental preclinical data. The present study was aimed at determining the therapeutic efficacy of retroviral gene transfer of IL-12 alone and in combination with HSVtk/GCV on the C6 glioma model. In initial studies, all the rats stereotactically injected with C6-IL12 cells survived longer than those injected with C6-neo cells, with 70% (4/6) surviving longer than 90 days. Rats were then co-injected i.c. with C6 cells and retroviral VPC carrying the different genes. The survival for the controls injected with VPC-neo cells was less than 30 days. Significant anti-tumor activity was observed with the VPC-IL12, VPCtk/GCV and VPC-IL12 + VPCtk/GCV (VPC-IL12+tk) groups (50%, 35% and 65% survival at 90 days, p