免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
用嵌合转换受体与分泌型陷阱靶向 TGFβ 以提升 T 细胞抗肿瘤活性
英文原题：Targeting TGFβ with chimeric switch receptor and secreted trap to improve T cells anti-tumor activity.
查看英文原题
Targeting TGFβ with chimeric switch receptor and secreted trap to improve T cells anti-tumor activity.
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研究概要
我们发现，靶向 TGF 通路可增强细胞免疫治疗。
中文摘要
方法
本研究设计了两种策略，以抵消TGF-β的作用，并使基因工程化T细胞在免疫抑制性肿瘤环境中获得功能优势。我们设计了基于TGF-β受体I的共刺激转换受体（CSRI），由TGF-β受体I胞外结合结构域和4-1BB共刺激信号结构域组成。此外，我们还测试了由T细胞产生的TGF-β结合型单链可变片段（scFv）陷阱的效力。
结果
我们证明，与黑色素瘤靶细胞共培养后，这两种策略均能增强肿瘤特异性T细胞细胞因子分泌、上调活化标志物并降低抑制性标志物。此外，CSRI和抗TGF-β陷阱在体内均表现出更强的抗肿瘤功能。
结论
总体而言，我们显示靶向TGF-β通路可增强细胞免疫疗法。
展开英文摘要原文
METHODS
In this study, we developed two approaches to counteract the effects of TGF and provide a functional advantage to genetically engineered T cells in the immunoinhibitory tumor milieu. We designed a TGF RI-based co-stimulatory switch receptor (CSRI), comprising the TGF receptor I extracellular binding domain and a 4-1BB co-stimulatory signaling moiety. Additionally, we tested the efficacy of a TGF -binding scFv trap produced by T cells.
RESULTS
We demonstrated that both approaches enhanced tumor-specific T cell cytokine secretion, upregulated activation markers, and reduced inhibition markers upon co-culture with melanoma targets. Furthermore, CSRI and the anti-TGF trap exhibited improved anti-tumor function in vivo .
CONCLUSION
Overall, we show that targeting the TGF pathway can enhance cellular immunotherapy.
论文信息
- 作者
- Matikhina T、Cohen CJ
- 单位
- The Laboratory of Tumor Immunology and Immunotherapy, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.Israel
- 期刊
- Frontiers in immunology2024
- 原文标识
- PubMed 39512355 · DOI 10.3389/fimmu.2024.1460266
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