Treatment > Immunotherapy

Meeting Abstract

Synergistic Antiglioma Activity of Interleukin-12 and Interleukin-18

Koji Adachi

Nippon Medical School, Tokyo, Japan

Background. Interleukin18 (IL-18), which was identified as a factor to stimulate interferon gamma production, is a novel member of cytokines with antitumor effect. 
Antitumor activity of IL-18 and IL-12, well-known antitumor cytokine, against glioma cells was examined using chromium release assay and animal model.

Method. (1) In vitro study: As target cells, we used mouse glioma cell line 203 labeled with 51Cr. 
Effectors were splenocytes from C57BL/6, from which 203 glioma was derived. 
The effector cells were treated with 10 ng/mL of mouse recombinant IL-18 and/or 1 ng/mL of mouse recombinant IL-12 for 3 hours. 
After washing, effectors and targets were mixed at ratios of 25 to 200. 
Cytotoxicity was calculated by a gamma counter. 
(2) In vivo study: 203 cells were inoculated in the backs of C57BL/6 mice and allowed to make subcutaneous tumors. 
After 10 days, IL-12 and/or IL-18 were injected intratumorally. 

Results. Augmentation of antitumor effect against glioma cells after IL-18, IL-12, and IL-18+IL-12 treatment was 2.7-fold, 1.7-fold, and 5.1-fold, respectively. 
In animal models, treatment of IL-18, IL-12, and IL-18+IL-12 showed permanent tumor reduction (83%) and disappearance (17%), transient tumor shrinkage, and complete disappearance, respectively. 

Conclusions. Treatment of splenocytes with IL-18 augmented the antitumor effect against glioma cells. 
IL-18 treatment showed antitumor effect in an animal model. 
IL-12 and IL-18 showed synergistic antitumor effect in vitro and in vivo.

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