{"title":"利用 SLdacA 增强肿瘤特异性免疫力:一种以 STING 通路为目标的减毒沙门氏菌介导的 c-di-AMP 递送系统。","authors":"","doi":"10.1016/j.ijpharm.2024.124759","DOIUrl":null,"url":null,"abstract":"<div><div>The STING agonist stimulates an anti-tumor immune response by activating T cells, but its limited tumor-targeting specificity poses risks of cytokine storms or autoimmune reactions. Conversely, attenuated <em>Salmonella typhimurium</em> △ppGpp (S.t△ppGpp) exhibits superior tumor-targeting specificity and potent anti-tumor immunogenicity. However, the anti-tumor effects of <em>Salmonella</em> carrying STING agonists remain underexplored. In this study, we engineered a strain called SL<sup>dacA</sup>, utilizing S.t△ppGpp as a carrier, to produce c-di-AMP. This engineered strain effectively enhances dendritic cell maturation and M1-type macrophage polarization by inducing type I interferon production, thereby recruiting and activating effector T cells against tumor progression. This process is regulated by the STING/type I interferon pathway. Our findings indicate that utilizing S.t△ppGpp as a delivery vehicle for STING agonists holds promise as a strategy for synergistic bacterial-mediated immunotherapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhancing Tumor-Specific immunity with SLdacA: A attenuated Salmonella-mediated c-di-AMP delivery system targeting the STING pathway\",\"authors\":\"\",\"doi\":\"10.1016/j.ijpharm.2024.124759\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The STING agonist stimulates an anti-tumor immune response by activating T cells, but its limited tumor-targeting specificity poses risks of cytokine storms or autoimmune reactions. Conversely, attenuated <em>Salmonella typhimurium</em> △ppGpp (S.t△ppGpp) exhibits superior tumor-targeting specificity and potent anti-tumor immunogenicity. However, the anti-tumor effects of <em>Salmonella</em> carrying STING agonists remain underexplored. In this study, we engineered a strain called SL<sup>dacA</sup>, utilizing S.t△ppGpp as a carrier, to produce c-di-AMP. This engineered strain effectively enhances dendritic cell maturation and M1-type macrophage polarization by inducing type I interferon production, thereby recruiting and activating effector T cells against tumor progression. This process is regulated by the STING/type I interferon pathway. Our findings indicate that utilizing S.t△ppGpp as a delivery vehicle for STING agonists holds promise as a strategy for synergistic bacterial-mediated immunotherapy.</div></div>\",\"PeriodicalId\":14187,\"journal\":{\"name\":\"International Journal of Pharmaceutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378517324009931\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378517324009931","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
STING 激动剂通过激活 T 细胞来刺激抗肿瘤免疫反应,但其有限的肿瘤靶向特异性会带来细胞因子风暴或自身免疫反应的风险。相反,减毒鼠伤寒沙门氏菌△ppGpp(S.t△ppGpp)具有更强的肿瘤靶向特异性和有效的抗肿瘤免疫原性。然而,携带 STING 激动剂的沙门氏菌的抗肿瘤作用仍未得到充分探索。在这项研究中,我们利用S.t△ppGpp作为载体,设计了一种名为SLdacA的菌株来产生c-di-AMP。这种工程菌株通过诱导I型干扰素的产生,有效地增强了树突状细胞的成熟和M1型巨噬细胞的极化,从而招募和激活效应T细胞对抗肿瘤的进展。这一过程受 STING/ I 型干扰素通路调控。我们的研究结果表明,利用S.t△ppGpp作为STING激动剂的递送载体有望成为细菌介导的协同免疫疗法的一种策略。
Enhancing Tumor-Specific immunity with SLdacA: A attenuated Salmonella-mediated c-di-AMP delivery system targeting the STING pathway
The STING agonist stimulates an anti-tumor immune response by activating T cells, but its limited tumor-targeting specificity poses risks of cytokine storms or autoimmune reactions. Conversely, attenuated Salmonella typhimurium △ppGpp (S.t△ppGpp) exhibits superior tumor-targeting specificity and potent anti-tumor immunogenicity. However, the anti-tumor effects of Salmonella carrying STING agonists remain underexplored. In this study, we engineered a strain called SLdacA, utilizing S.t△ppGpp as a carrier, to produce c-di-AMP. This engineered strain effectively enhances dendritic cell maturation and M1-type macrophage polarization by inducing type I interferon production, thereby recruiting and activating effector T cells against tumor progression. This process is regulated by the STING/type I interferon pathway. Our findings indicate that utilizing S.t△ppGpp as a delivery vehicle for STING agonists holds promise as a strategy for synergistic bacterial-mediated immunotherapy.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.