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An engineered IL-21 variant is a potent antitumor candidate for antitumor immunotherapy

   
@article{APS11476,
	author = {Hui Wu and Ya-ping Cheng and Yu-long Liu and Ruo-han Zhu and Li-wen Ji and Ming-kai Wang and Quan-xiao Li and Zhao-ling Shen and Tian-lei Ying and Yan-ling Wu},
	title = {An engineered IL-21 variant is a potent antitumor candidate for antitumor immunotherapy},
	journal = {Acta Pharmacologica Sinica},
	volume = {47},
	number = {3},
	year = {2026},
	keywords = {},
	abstract = {IL-21, as an immune agonist, has demonstrated limited therapeutic efficacy in cancer immunotherapy. To overcome this inherent limitation, we constructed a yeast surface-displayed IL-21 mutant library guided by the structure of the IL-21/IL-21 receptor (IL-21R). Following one round of magnetic bead sorting and three rounds of fluorescence-activated cell sorting, several variants were isolated and evaluated for receptor-binding affinity at the protein level. We identified an IL-21 Variant (IL-21V) featuring four critical mutations (Q19L, Y23N, V69T and K73Q) at the interaction interface with IL-21R. Compared with wild-type IL-21, IL-21V exhibited an approximately 7-fold increase in IL-21R binding affinity and a ~50-fold increase in STAT3 signalling pathway activation. In preclinical in vivo models, IL-21V exhibited broad-spectrum antitumor activity against B16F10 melanoma, MC38, and CT26 colorectal cancer. Notably, IL-21V exhibited significantly stronger antitumor effects compared to wild-type IL-21, even at a low dose of 0.15 mg/kg, highlighting its potential as a promising and effective immunotherapeutic candidate for cancer treatment.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/11476}
}