一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
携带 GM-CSF 的溶瘤腺病毒增强 T 细胞浸润并抑制局部和远端肿瘤生长
英文原题：GM-CSF Armed Oncolytic Adenovirus Enhances T-Cell Infiltration and Suppresses Local and Distal Tumor Growth.
查看英文原题
GM-CSF Armed Oncolytic Adenovirus Enhances T-Cell Infiltration and Suppresses Local and Distal Tumor Growth.
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中文摘要
免疫系统对实体瘤的浸润能力有限，这归因于免疫抑制性肿瘤微环境（TME），这仍然是癌症治疗中的一个重大挑战。溶瘤腺病毒（OAd）除了诱导先天性和适应性免疫反应外，还能直接杀死肿瘤细胞。因此，使用OAd治疗肿瘤是一种有吸引力的方法。在本研究中，我们构建了一种携带人粒细胞-巨噬细胞集落刺激因子（GM-CSF）的OAd，由E2F启动子控制，即Ad5/3-E2F-d24-GM-CSF（命名为OAd-Z1）。在体外和体内测试了OAd的抗肿瘤活性。这些发现表明，OAd表达GM-CSF，在肿瘤细胞中有效复制，抑制肿瘤生长，激活从头抗肿瘤反应，促进肿瘤细胞凋亡和免疫原性细胞死亡，并在体外和体内增加细胞因子和趋化因子的产生。此外，OAd在体内表现出远隔效应并刺激T淋巴细胞浸润。我们的发现表明，OAd-Z1代表了有前景的肺癌免疫治疗候选药物，具有增强全身抗肿瘤免疫的潜力。
展开英文摘要原文
The limited ability of the immune system to infiltrate solid tumors, attributed to the immunosuppressive tumor microenvironment (TME), remains a significant challenge in cancer therapy oncolytic adenovirus (OAd) that can directly kill tumor cells in addition to inducing both innate and adaptive immune responses.
Therefore, the use of OAd to treat tumors is an appealing approach. In this study, we engineered an OAd armed with a human granulocyte-macrophage colony-stimulating factor (GM-CSF), controlled by the E2F promoter, Ad5/3-E2F-d24-GM-CSF (named OAd-Z1). The antitumor activity of OAd was tested in vitro and in vivo.
These findings demonstrated that OAd expressed GM-CSF, replicated effectively in tumor cells, inhibited tumor growth, activated the de novo antitumor response, promoted apoptosis and immunogenic cell death in tumor cells, and increased cytokine and chemokine production both in vitro and in vivo.
Additionally, OAd demonstrated an abscopal effect and stimulated T lymphocyte infiltration in vivo.
Our findings demonstrate that OAd-Z1 represents promising immunotherapeutic candidates for lung cancer, with the potential to enhance systemic antitumor immunity.
论文信息
- 作者
- Xu HW、Wang QW、Zhao M、Jun J、Shu RG、Shi YS、Peng XL、Yu JM
- 单位
- College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China.China
- 期刊
- Viruses2026 Jan 12
- 原文标识
- PubMed 41600865 · DOI 10.3390/v18010102
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