Dissimilar anti-tumour reactions induced by tumour cells engineered with the interleukin-2 or interleukin-15 gene in nude mice
✍ Scribed by Di Carlo, Emma; Meazza, Raffaella; Basso, Stefania; Rosso, Ombretta; Comes, Alberto; Gaggero, Alessia; Musiani, Piero; Santi, Leonardo; Ferrini, Silvano
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 330 KB
- Volume
- 191
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
Interleukin (IL)-15 shares immuno-stimulatory properties with IL-2 and is a potent inducer of natural killer (NK) cell function. The major histocompatibility complex (MHC) class I-negative human small cell lung cancer (SCLC) cell line N592, engineered to express a modi®ed IL-15 cDNA (N592/IL-15), secreted biologically active IL-15 (300±500 pg/ml), capable of boosting T-cell proliferation and NK activity in vitro'. The effect of IL-15 gene transfer on natural immunity in vivo' was assessed by xenotransplants in nude mice and compared with that of the IL-2 gene. N592 cells engineered with IL-2 (N592/IL-2) were promptly rejected, while N592/IL-15 displayed a signi®cant delay in tumour growth and a slightly reduced take rate. However, in NK-depleted nude mice, N592/IL-15 displayed the same growth kinetics as unmodi®ed N592 cells, and N592/IL-2 grew with slightly reduced kinetics. An impressive reactive cell in®ltration, consisting mainly of macrophages and granulocytes, was associated with N592/IL-2 tumour rejection, while a more evident recruitment of NK cells was found in N592/IL-15 tumours. In both N592 transfected tumours, we found expression of chemoattractant molecules, such as granulocyte macrophagecolony stimulating factor (GM-CSF) and monocyte chemoattractant protein (MCP)-1, while macrophage in¯ammatory protein (MIP)-2 was produced by endothelial cells only in N592/IL-2 tumours. In this tumour, very few and severely damaged microvessels were found, while microvessels were numerous in N592/IL-15 tumours. The potent recruitment of NK cells mediated by IL-15 gene transfer suggests its possible therapeutic use in tumours lacking MHC class I.