Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma
Jinfang Cui, Yuchao He, Fuyi Zhu, Wenchen Gong, Ran Zuo, Yu Wang, Yi Luo, Liwei Chen, Chengmeng Wang, Gengwei Huo, Hailing Lu, Zhiyong Liu, Peng Chen, Hua Guo
Abstract
, we found that the combination of inetetamab and cisplatin induced synergistic effects, including induction of pyroptosis, in LUAD. Mechanistic studies revealed that inetetamab combined with cisplatin inhibited HER2/AKT/Nrf2 signaling to increase ROS levels, which triggered NLRP3/caspase-1/GSDMB-mediated pyroptosis to synergistically enhance antitumor efficacy in LUAD cells. In addition, cisplatin enhanced the PBMC-killing ability of inetetamab by inducing GSDMB-mediated pyroptosis, which can be explained by increased secretion of IFN-γ. Our study reveals that the anti-HER2 monoclonal antibody inetetamab may be an attractive candidate for LUAD therapy, which opens new avenues for therapeutic interventions for LUAD.