Equipping Natural Killer Cells with Cetuximab through
Metabolic Glycoengineering and Bioorthogonal Reaction for Targeted
Treatment of KRAS Mutant Colorectal Cancer
posted on 2021-04-08, 14:04authored byXianwu Wang, Xi Luo, Yunpeng Tian, Ting Wu, Jian Weng, Zhu Li, Feng Ye, Xuefei Huang
While
Cetuximab can be used to treat KRAS wild-type colon cancer
cells by targeting EGFR and inhibiting the activation of downstream
signaling pathways, it exhibits little therapeutic effect on KRAS
mutant colon cancer cells. Natural killer (NK) cells are a class of
powerful immune cells with anticancer activities. However, NK cells
typically lack inherent tumor targeting abilities. Here, a new method
is established to bestow NK-92 cells with tumor targeting abilities
by installing cetuximab on the cell surface. Through metabolic glycoengineering,
azide groups were introduced onto the surface of NK-92 cells. Bioorthogonal
strain promoted the azide–alkyne cycloaddition click reaction
of engineered NK-92 cells with alkyne modified cetuximab functionalized
NK cells with the antibody. The resulting NK-92 cells were significantly
more effective than the parent NK-92 cells in protecting against tumor
development in a KRAS mutant mouse tumor model resistant to cetuximab
treatment. Thus, NK cell functionalization with antibodies enabled
by metabolic glycoengineering is a promising strategy to enhance anticancer
immune therapy.