Song Yinhong, Liu Yalan, Hu Rong, Su Min, Rood Debra, Lai Laijun
Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut. Medical College, Three Gorges University, Yichang, China.
Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut.
Mol Cancer Ther. 2016 Oct;15(10):2413-2421. doi: 10.1158/1535-7163.MCT-16-0111. Epub 2016 Jul 29.
Both IL7 and IL15 have become important candidate immunomodulators for cancer treatment. However, IL7 or IL15 used alone suffers from shortcomings, such as short serum half-life and limited antitumor effect. We have cloned and expressed a recombinant (r) IL7/IL15 fusion protein in which IL7 and IL15 are linked by a flexible linker. We then compared the antitumor effect of rIL7/IL15 with the individual factors rIL7 and/or rIL15. We show here that rIL7/IL15 has a higher antitumor activity than the combination of the individual factors in both murine B16F10 melanoma and CT-26 colon cancer models. This was associated with a significant increase in tumor infiltration of T cells, DCs, and NK cells and a decrease in regulatory T cells (Tregs). In addition, rIL7/IL15-treated DCs had higher expression of costimulatory molecules CD80 and CD86. The higher antitumor activity of rIL7/IL15 is likely due to its longer in vivo half-life and different effects on immune cells. Our results suggest that rIL7/IL15 may offer a new tool to enhance antitumor immunity and treat cancer. Mol Cancer Ther; 15(10); 2413-21. ©2016 AACR.
白细胞介素7（IL7）和白细胞介素15（IL15）均已成为癌症治疗的重要候选免疫调节剂。然而，单独使用IL7或IL15存在缺陷，如血清半衰期短和抗肿瘤作用有限。我们克隆并表达了一种重组（r）IL7/IL15融合蛋白，其中IL7和IL15通过柔性接头连接。然后，我们比较了rIL7/IL15与单个因子rIL7和/或rIL15的抗肿瘤作用。我们在此表明，在小鼠B16F10黑色素瘤和CT-26结肠癌模型中，rIL7/IL15比单个因子组合具有更高的抗肿瘤活性。这与肿瘤浸润的T细胞、树突状细胞（DCs）和自然杀伤细胞（NK细胞）显著增加以及调节性T细胞（Tregs）减少有关。此外，经rIL7/IL15处理的DCs共刺激分子CD80和CD86的表达更高。rIL7/IL15更高的抗肿瘤活性可能归因于其更长的体内半衰期以及对免疫细胞的不同作用。我们的结果表明，rIL7/IL15可能为增强抗肿瘤免疫力和治疗癌症提供一种新工具。《分子癌症治疗》；15(10)；2413 - 2421。©2016美国癌症研究协会。
