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An oncolytic virus–T cell chimera for cancer immunotherapy

Nat Biotechnol .. 2024-02; 
Yuxuan Chen , Xiaohong Chen , Weier Bao , Gang Liu , Wei Wei , Yuan Ping
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摘要

The efficacy of oncolytic adenoviruses (OAs) for cancer therapy has been limited by insufficient delivery to tumors after systemic injection and the propensity of OAs to induce the expression of immune checkpoints. To address these limitations, we use T cells to deliver OAs into tumors and engineer the OA to express a Cas9 system targeting the PDL1 gene encoding the immune checkpoint protein PD-L1. By cloaking OAs with cell membranes presenting T cell-specific antigens, we physically conjugated OAs onto T cell surfaces by antigen-receptor interaction. We tested the oncolytic virus-T cell chimera (ONCOTECH) via intravenous delivery in mouse cancer models, including models of melanoma, pancreatic adenocarcinoma, ... More

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