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

Abstract

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.

Antitumor effects of the combination therapy with TNF-α gene–modified tumor cells and interleukin 12 in a melanoma model in mice

“…20 The effectiveness of IL -12 and tumor-cell -based vaccines in the treatment of established tumors have been tested in several recently published reports. In two of them, IL -2 gene ±transduced tumor cells were used in conjunction with IL -12 to treat glioma 32 or colon adenocarcinoma. 33 In both studies the combined therapy produced better results than the treatment with either agent alone and led to a long -term survival of double -treated mice.…”

Efficient cotransduction of tumors by multiple herpes simplex vectors: Implications for tumor vaccine production

“…Combination therapy with vaccination using irradiated glioma cells engineered to produce IL-2 and systemic recombinant IL-12 has proved to be more effective than recombinant IL-12 treatment alone. 48 Experiments in a murine renal cell carcinoma model showed that the systemic administration of IL-2 and IL-12 had greater antitumoral efficacy than either IL-2 or IL-12 alone. 49 We took advantage of the ability of HSV vectors to cotransduce cells with high efficiency to evaluate the effects of tumor vaccines secreting the combination of IL-2 and IL-12 on hepatic tumor growth and to further validate the practicality of multiple gene delivery.…”

Enhanced inhibition of syngeneic murine tumors by combinatorial therapy with genetically engineered HSV-1 expressing CCL2 and IL-12

“…40 Its proinflammatory effects that do not rely on an intact IL-2 receptor pathway have been suggested as a potentially important approach for immunotherapy.…”