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HVJ-E 联合 T 细胞共刺激分子刺激的局部治疗可诱导全身抗肿瘤效应

英文原题:Local treatment of HVJ-E with T cell costimulatory molecule stimulation elicits systemic anti-tumor effects.

查看英文原题

Local treatment of HVJ-E with T cell costimulatory molecule stimulation elicits systemic anti-tumor effects.

PubMed 2024/10/10(内容时间) Mol Ther Oncol Q1 · IF 8.5(JCR 2025)

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中文摘要

TIL(肿瘤浸润淋巴细胞)是控制肿瘤生长的关键因素。人们需要能够活化TIL的治疗方法,以治疗转移性肿瘤患者。本研究显示,在多种癌细胞系中,局部肿瘤接受经紫外线照射的血凝性日本脑炎病毒包膜(HVJ-E)与激动性抗体(包括针对T细胞共刺激分子OX40的抗体)联合治疗,可通过依赖T细胞的方式诱导全身性抗肿瘤效应。转录组和T细胞受体库分析显示,HVJ-E联合抗OX40抗体可活化CD4和CD8 T细胞,并促进T细胞在不同肿瘤间迁移。这些全身性抗肿瘤效应依赖NKG2D与其配体之间的结合。我们的发现揭示了诱导全身性抗肿瘤效应的机制,可为开发诱发此类效应的治疗策略提供帮助。

展开英文摘要原文

The tumor-infiltrating lymphocyte (TIL) is a crucial factor in controlling tumor growth. A therapeutic method activating TIL is desired for treating patients with metastatic tumors.

Here, we show that treating a local tumor with a combination therapy of UV-irradiated hemagglutinating virus of Japan envelope (HVJ-E) plus agonist antibodies, including OX40, against T cell costimulatory molecules induces systemic anti-tumor effects in a T cell-dependent manner in multiple cancer cell lines.

Transcriptome and T cell receptor repertoire analyses revealed that HVJ-E + anti-OX40 antibody treatment activates CD4 and CD8 T cells and promotes T cell trafficking between tumors. These systemic anti-tumor effects required an association between Nkg2d and Nkg2d ligands.

Our findings provide insights into how systemic anti-tumor effects are induced and may help the development of therapeutic strategies for eliciting such effects.

论文信息

作者
Ishibashi A、Li Y、Hisatomi Y、Ohta N、Uegaki Y、Tanemura A、Ohashi R、Kitamura K
单位
Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Japan
期刊
Molecular therapy. Oncology2024 Dec 19
原文标识
PubMed 39534532 · DOI 10.1016/j.omton.2024.200893