Hyperacute rejection-engineered oncolytic virus for interventional clinical trial in refractory cancer patients

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2025-01-17 DOI:10.1016/j.cell.2024.12.010

Liping Zhong, Lu Gan, Bing Wang, Tao Wu, Fei Yao, Wenlin Gong, Hongmei Peng, Zhiming Deng, Guoyou Xiao, Xiyu Liu, Jintong Na, Desong Xia, Xianjun Yu, Zhikun Zhang, Bangde Xiang, Yu Huo, Dan Yan, Zhixin Dong, Fang Fang, Yun Ma, Yongxiang Zhao

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引用次数: 0

Abstract

Recently, oncolytic virus (OV) therapy has shown great promise in treating malignancies. However, intravenous safety and inherent lack of immunity are two significant limitations in clinical practice. Herein, we successfully developed a recombinant Newcastle disease virus with porcine α1,3GT gene (NDV-GT) triggering hyperacute rejection. We demonstrated its feasibility in preclinical studies. The intravenous NDV-GT showed superior ability to eradicate tumor cells in our innovative CRISPR-mediated primary hepatocellular carcinoma monkeys. Importantly, the interventional clinical trial treating 20 patients with relapsed/refractory metastatic cancer (Chinese Clinical Trial Registry of WHO, ChiCTR2000031980) showed a high rate (90.00%) of disease control and durable responses, without serious adverse events and clinically functional neutralizing antibodies, further suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of NDV-GT for immunovirotherapy. Collectively, our results demonstrate the high safety and efficacy of intravenous NDV-GT, thus providing an innovative technology for OV therapy in oncological therapeutics and beyond.

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超急性排斥工程溶瘤病毒在难治性癌症患者中的介入临床试验

近年来，溶瘤病毒（OV）疗法在治疗恶性肿瘤方面显示出巨大的前景。然而，静脉注射安全性和先天缺乏免疫力是临床实践中的两个重大限制。本研究成功构建了含有猪α 1,3gt基因（NDV-GT）的重组新城疫病毒，该病毒可引发超急性排斥反应。我们在临床前研究中证明了其可行性。在我们创新的crispr介导的原发性肝细胞癌猴子中，静脉注射NDV-GT显示出卓越的根除肿瘤细胞的能力。重要的是，对20例复发/难治性转移性癌症患者进行的干预性临床试验（WHO中国临床试验注册，ChiCTR2000031980）显示，疾病控制率高（90.00%），反应持久，无严重不良事件和临床功能性中和抗体，进一步表明在这些条件下免疫原性极小，证明了NDV-GT用于免疫病毒治疗的可行性。总的来说，我们的研究结果表明静脉注射NDV-GT具有很高的安全性和有效性，从而为肿瘤治疗及其他领域的OV治疗提供了一种创新技术。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.

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