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Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-12-02 , DOI: 10.1084/jem.20190801
Xiaodong Jiang 1 , Viswanathan Muthusamy 2 , Olga Fedorova 3, 4 , Yong Kong 5 , Daniel J Kim 1 , Marcus Bosenberg 6 , Anna Marie Pyle 4, 7, 8 , Akiko Iwasaki 3, 4, 6, 9
Affiliation  

Cytosolic nucleic acid–sensing pathways can be triggered to enhance immune response to cancer. In this study, we tested the antitumor activity of a unique RIG-I agonist, stem loop RNA (SLR) 14. In the immunogenic tumor models, we observed significant tumor growth delay and an extended survival in SLR14-treated mice. SLR14 also greatly improved antitumor efficacy of anti-PD1 antibody over single-agent treatment. SLR14 was mainly taken up by CD11b+ myeloid cells in the tumor microenvironment, and many genes associated with immune defense were significantly up-regulated after treatment, accompanied by increase in the number of CD8+ T lymphocytes, NK cells, and CD11b+ cells in SLR14-treated tumors. Strikingly, SLR14 dramatically inhibited nonimmunogenic B16 tumor growth, and the cured mice developed an immune memory. Furthermore, a systemic antitumor response was observed in both bilateral and tumor metastasis models. Collectively, our results demonstrate that SLR14 is a promising therapeutic RIG-I agonist for cancer treatment, either alone or in combination with existing immunotherapies.



中文翻译:


RIG-I 激动剂 SLR14 的瘤内递送可诱导强烈的抗肿瘤反应。



可以触发细胞质核酸传感途径来增强对癌症的免疫反应。在这项研究中,我们测试了一种独特的 RIG-I 激动剂茎环 RNA (SLR) 14 的抗肿瘤活性。在免疫原性肿瘤模型中,我们观察到 SLR14 治疗的小鼠肿瘤生长明显延迟,存活时间延长。与单药治疗相比,SLR14 还大大提高了抗 PD1 抗体的抗肿瘤功效。 SLR14主要被肿瘤微环境中的CD11b +骨髓细胞摄取,治疗后许多与免疫防御相关的基因显着上调,伴随着肿瘤微环境中CD8 + T淋巴细胞、NK细胞和CD11b +细胞数量的增加。 SLR14 治疗的肿瘤。引人注目的是,SLR14 显着抑制非免疫原性 B16 肿瘤生长,并且治愈的小鼠产生了免疫记忆。此外,在双侧模型和肿瘤转移模型中均观察到全身抗肿瘤反应。总的来说,我们的结果表明,SLR14 是一种有前途的治疗性 RIG-I 激动剂,可单独或与现有免疫疗法联合用于癌症治疗。

更新日期:2019-12-02
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