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1篇 您的检索式:作者名="Ethan J.Blumenthal"
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1Engineered extracellular vesicles for concurrent Anti-PDL1 immunotherapy and chemotherapy显示文摘Immune checkpoint inhibitors(ICI)targeting PD-1/PD-L1 have been approved for the treatment of a variety of cancers.However,the efficacy of antibody-based ICIs could be further improved by mitigating anti-drug antibodies,proteolytic cleavage,and on-target off-tumor toxicity.One strategy for accomplishing this is through the use of extracellular vesicles(EVs),cell derived submicron vesicles with many unique properties.We constructed an engineered MDA-MB-231 cell line for harvesting EVs.This was accomplished by overexpressing a high-affinity variant human PD-1 protein(havPD-1),while simultaneously knocking out intrinsic PD-L1 and beta-2 microglobulin.The engineered havPD-1 EVs reduced PD-L1 overexpressing cancer cell proliferation and induced cellular apoptosis.Moreover,the EVs were shown to efficiently block PD-L1 mediated T cell suppression.Meanwhile antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not observed.The havPD-1 EVs treatment resulted in robust anti-tumor activity in both preventative co-implantation and therapeutic xenograft tumor models reconstituted with human T cells.The efficacy of the havPD-1 EVs was shown to be comparable to clinical anti-PD1 monoclonal antibodies.Additionally,loading the havPD-1 EVs with a potent PARP inhibitor was shown to further augment treatment efficacy.In brief,the engineered universal EVs harboring havPD-1 proteins can be used for cancer concurrent immunotherapy and chemotherapy.Yundi Chen Lixue Wang Mingfeng Zheng Chuandong Zhu Guosheng Wang Yiqiu Xia Ethan J.Blumenthal Wenjun Mao Yuan Wan 2022Bioactive Materials2022,7,3:1
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