Inhibition of autophagy potentiated the anti-tumor effects of VEGF and CD47 bispecific therapy in glioblastoma

Applied Microbiology and Biotechnology
Xuyao ZhangDianwen Ju

Abstract

Glioblastoma, characterized by extensive microvascular proliferation and invasive tumor growth, is one of the most common and lethal malignancies in adults. Benefits of the conventional anti-angiogenic therapy were only observed in a subset of patients and limited by diverse relapse mechanism. Fortunately, recent advances in cancer immunotherapy have offered new hope for patients with glioblastoma. Herein, we reported a novel dual-targeting therapy for glioblastoma through simultaneous blockade of VEGF and CD47 signaling. Our results showed that VEGFR1D2-SIRPαD1, a VEGF and CD47 bispecific fusion protein, exerted potent anti-tumor effects via suppressing VEGF-induced angiogenesis and activating macrophage-mediated phagocytosis. Meanwhile, autophagy was activated by VEGFR1D2-SIRPαD1 through inactivating Akt/mTOR and Erk pathways in glioblastoma cells. Importantly, autophagy inhibitor or knockdown of autophagy-related protein 5 potentiated VEGFR1D2-SIRPαD1-induced macrophage phagocytosis and cytotoxicity against glioblastoma cells. Moreover, suppression of autophagy led to increased macrophage infiltration, angiogenesis inhibition, and tumor cell apoptosis triggered by VEGF and CD47 dual-targeting therapy, thus eliciting enhanced...Continue Reading

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Citations

Sep 6, 2019·Cellular Oncology (Dordrecht)·Seyed Mohammad Gheibi HayatAmirhossein Sahebkar
Aug 29, 2020·Advanced Materials·Yuqiong XiaXiaoyuan Chen
Aug 1, 2020·BioMed Research International·Manman DouYingqi Xing
Dec 18, 2020·Frontiers in Immunology·Jinyang HuBaofeng Wang
Feb 20, 2021·Journal of Cellular and Molecular Medicine·Xiaobo LuoQianming Chen
Jul 19, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Yuanyang WangWeibin Wang
Jul 25, 2021·Cancers·Chirayu R ChokshiSheila K Singh

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Datasets Mentioned

BETA
MG920788

Methods Mentioned

BETA
flow cytometry
Assay
confocal microscopy
xenograft

Software Mentioned

ID
Cyto
GraphPad Prism
Image J

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