Anti‐tumor activity of interleukin‐2‐producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system

Interleukin 12 (IL‐12) exhibits anti‐tumor activity in a variety of laboratory models. Although IL‐12 itself activates strong anti‐tumor activity, the combination of vaccine therapy with IL‐2‐transduced tumor cells and systemic rIL‐12 has been shown to cure tumor‐bearing mice more effectively than either rIL‐12 or IL‐2‐transduced tumor vaccines alone. In the present study, regression of brain tumors established in naive mice was obtained by combined administration of an intratumoral injection of a single dose of IL‐2‐producing glioma cells (SR/IL‐2 cells) and recombinant IL‐12. Intraperitoneal rIL‐12 administration substantially delayed the growth of s.c. inoculated gliomas, but not of gliomas located in the brain. Although vaccination with SR/IL‐2 cells alone was not effective against s.c. inoculated gliomas, the combination therapy of vaccination with irradiated SR/IL‐2 cells and systemic rIL‐12 was more effective than rIL‐12 alone. In our brain‐tumor model, intratumoral administration of irradiated SR/IL‐2 cells and of rIL‐12 remarkably prolonged survival as compared with untreated mice. Efficacy was reduced when studies were performed in mice depleted of CD8+ cells or NK cells. Mice cured of their intracerebral tumors by combined administration of SR/IL‐2 cells and rIL‐12 demonstrated protective immunity upon rechallenge. In summary, the therapeutic potential for control of tumor growth by intratumoral administration of IL‐2‐producing glioma cells and rIL‐12 may be useful in the development of treatment for patients with glioma. Int. J. Cancer 80:425–430, 1999. © 1999 Wiley‐Liss, Inc.