Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy
Fang Xu, Dongpeng Jiang, Jialu Xu, Huaxing Dai, Qin Fan, Ziying Fei, Beilei Wang, Yue Zhang, Qingle Ma, Qianyu Yang, Yitong Chen, Edikan A. Ogunnaike, Jianhong Chu, Chao Wang
Abstract
Advances in the development of therapeutic extracellular vesicles (EVs) for cancer immunotherapy have allowed them to emerge as an alternative to cell therapy. In this proof-of-concept work, we develop bispecific EVs (BsEVs) by genetically engineering EV-producing dendritic cells (DCs) with aCD19 scFv and PD1 for targeting tumor antigens and blocking immune checkpoint proteins simultaneously. We find that these bispecific EVs (EVs-PD1-aCD19) have an impressive ability to accumulate in huCD19-expressing solid tumors following intravenous injection. In addition, EVs-PD1-aCD19 can remarkably reverse the immune landscape of the solid tumor by blocking PD-L1. Furthermore, EVs-PD1-aCD19 can also target tumor-derived EVs in circulation, which prevents the formation of a premetastatic niche in other tissues. Our technology is a demonstration of bispecific EV-based cancer immunotherapy, which may inspire treatments against various types of tumors with different surface antigens and even a patient-tailored therapy.