Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody----中国科学院微生物研究所

科研成果

论文题目:	Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody
作者:	Zhang Ge, Liu Rongzhi, Zhu Xuekai, Wang Lei, Ma Juan, Han Huamin, Wang Xiaomin, Zhang Ganlin, He Wen, Wang Wei, Liu Changzhen, Li Shenghua, Sun Meiyi, Gao Bin*
联系作者:	Gao Bin*
刊物名称:	Immunology and cell biology
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年份:	2013
影响因子:	3.811
论文下载:	http://www.nature.com/icb/journal/vaop/ncurrent/full/icb201345a.html
摘要:	The efficacy of immunotherapy based on natural killer (NK) cells is hampered by intrinsic non-specific cytotoxicity and insufficient activation of NK cells. Here, we confer the T-cell receptor-like (TCR-like) specificity on NK cells, taking advantage of both the innate and adaptive immune arms of the immune response to generate enhanced anti-melanoma activity. The TCR-like antibody (Ab) GPA7 was selected against melanoma-associated gp100/human leukocyte antigen (HLA)-A2 complex and then fused to intracellular domain of CD3-zeta chain. This fusion construct was incorporated into NK-92MI cell line and expressed as a chimeric antigen receptor on the surface of the cell. The anti-tumour activity of the transgenic NK-92MI-GPA7-zeta cell line was assessed against melanoma in vitro and in vivo. The engineered NK-92MI-GPA7-zeta cells could recognize melanoma cells in the context of HLA-A2 and showed enhanced killing of both melanoma cell lines and primary melanoma. Furthermore, adoptively transferred NK-92MI-GPA7-zeta cells significantly suppressed the growth of human melanoma in a xenograft model in mice. Collectively, these results demonstrate that the TCR-like Ab, GPA7, could redirect NK cells to target the intracellular antigen gp100 and enhance anti-melanoma activity, providing a promising immunotherapeutic strategy to prevent and treat melanoma.Immunology and Cell Biology advance online publication, 8 October 2013; doi:10.1038/icb.2013.45.