CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
STING 激动剂 IMSA101 通过诱导 IL-18 分泌增强 CAR-T 细胞功能
英文原题：The STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion.
查看英文原题
The STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion.
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中文摘要
作为提高针对实体瘤的CAR-T 细胞治疗成功率的一种策略，我们在此测试了CAR-T 与IMSA101（一种新开发的干扰素基因刺激因子（STING）激动剂）的联合使用。在两种同基因肿瘤模型中，当小鼠在静脉输注CAR-T 之外还接受瘤内注射IMSA101治疗时，观察到总生存期改善。对从肿瘤中分离的CAR-T 进行的转录组分析显示，在联合治疗组中T细胞活化升高，以及细胞因子通路特征上调，特别是IL-18。此外，IMSA101治疗在血清和肿瘤中检测到更高水平的IL-18。与此一致的是，使用IL-18受体阴性的CAR-T 会损害接受联合治疗小鼠的抗肿瘤反应。总之，我们发现IMSA101增强CAR-T 功能，这是通过STING激动剂诱导的IL-18分泌所促进的。
展开英文摘要原文
As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion.
Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion.
论文信息
- 作者
- Uslu U、Sun L、Castelli S、Finck AV、Assenmacher CA、Young RM、Chen ZJ、June CH
- 第一作者单位
- Center for Cellular Immunotherapies, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.United States
- 通讯作者单位
- Center for Cellular Immunotherapies, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. cjune@upenn.edu.United States
- 文献类型
- 非美国政府资助研究
- 期刊
- Nature communications2024 May 10
- 原文标识
- PubMed 38730243 · DOI 10.1038/s41467-024-47692-9
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