Localization of Salmonella and albumin-IL-2 to the tumor microenvironment augments anticancer T cell immunity.
Localization of Salmonella and albumin-IL-2 to the tumor microenvironment augments anticancer T cell immunity.
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DOI：
10.1186/s12929-022-00841-y
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发表时间：
2022-08-12
影响因子：
11
通讯作者：
Hung, Chien-Fu
中科院分区：
文献类型：
--
作者：
Kung, Yu-Jui;Lam, Brandon;Tseng, Ssu-Hsueh;MacDonald, Alana;Tu, Hsin-Fang;Wang, Suyang;Lin, John;Tsai, Ya Chea;Wu, T. C.;Hung, Chien-Fu
几个世纪以来，人们一直在研究基于微生物的制剂作为治疗癌症的治疗方式。理论上，这些方法生产成本低廉，广泛适用于多种癌症类型，并且可以与其他癌症治疗策略产生协同作用。我们的目的是评估沙门氏菌 SL7207 与白细胞介素 2 (IL-2)（一种有效的免疫刺激剂）联合使用微生物疗法治疗小鼠结肠癌的疗效。雌性 BALB/c 小鼠皮下植入 CT26 肿瘤（结肠癌模型）。选择荷瘤小鼠并给予融合蛋白白蛋白-IL-2（Alb-IL2），以进一步分析抗癌效果。我们证明，沙门氏菌 SL7207（鼠伤寒沙门氏菌血清型的一种转基因菌株）优先在肿瘤微环境中积聚，增强其刺激局部先天免疫的能力。我们以融合蛋白 Alb-IL2 的形式递送 IL-2，我们证明它具有优先积累特性，将其带到肿瘤和次级淋巴器官。与对照组相比，用沙门氏菌 +Alb-IL2 治疗荷瘤小鼠可实现更好的肿瘤控制并提高总体生存率。当评估有助于我们观察到的肿瘤控制的免疫因素时，在用沙门氏菌 + Alb-IL2治疗的小鼠中观察到具有优异效应功能的T细胞群显着增强。我们通过抗体介导的 T 细胞耗竭实验证实，这些 T 细胞对于观察到的肿瘤控制是不可或缺的。这些发现强调了沙门氏菌 +Alb-IL2作为一种新型治疗方法的能力，可诱导T细胞介导的抗肿瘤免疫并在小鼠癌症模型中发挥长期肿瘤控制作用。在线版本包含可在 10.1186/s12929-022-00841-y 获取的补充材料。
For centuries, microbial-based agents have been investigated as a therapeutic modality for the treatment of cancer. In theory, these methods would be cheap to produce, broadly applicable in a wide array of cancer types, and could synergize with other cancer treatment strategies. We aimed to assess the efficacy of combining microbial-based therapy using Salmonella SL7207 with interleukin-2 (IL-2), a potent immunostimulatory agent, in the treatment of murine colon carcinoma. Female BALB/c mice were implanted subcutaneously with CT26 tumors, a model of colon carcinoma. Mice bearing tumors were selected and administered Albumin-IL-2 (Alb-IL2), a fusion protein, for further analysis of anticancer effect. We demonstrated that Salmonella SL7207, a genetically modified strain of Salmonella enterica serovar Typhimurium, preferentially accumulates in the tumor microenvironment, potentiating it to stimulate localized innate immunity. We delivered IL-2 as a fusion protein, Alb-IL2, which we demonstrate to have preferential accumulation properties, bringing it to the tumor and secondary lymphoid organs. Treatment of tumor-bearing mice with Salmonella + Alb-IL2 leads to superior tumor control and enhanced overall survival compared to controls. When assessing immunological factors contributing to our observed tumor control, significantly enhanced T cell population with superior effector function was observed in mice treated with Salmonella + Alb-IL2. We confirmed that these T cells were indispensable to the observed tumor control through antibody-mediated T cell depletion experiments. These findings highlight the ability of Salmonella + Alb-IL2 to serve as a novel therapeutic approach to induce T cell-mediated antitumor immunity and exert long-term tumor control in a murine model of cancer. The online version contains supplementary material available at 10.1186/s12929-022-00841-y.
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DOI：
10.1084/jem.188.12.2357
发表时间：
1998-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hung K;Hayashi R;Lafond-Walker A;Lowenstein C;Pardoll D;Levitsky H
通讯作者：
Levitsky H
影响因子：
45.3
作者：
FYFE, G;FISHER, RI;LOUIE, AC
通讯作者：
LOUIE, AC
DOI：
10.1128/genomea.01591-16
发表时间：
2017-02-02
期刊：
Genome announcements
影响因子：
--
作者：
Johnson SA;Ormsby MJ;Wall DM
通讯作者：
Wall DM
DOI：
10.4049/jimmunol.1490019
发表时间：
2014-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
11.5
作者：
Desai, N;Trieu, V;Soon-Shiong, P
通讯作者：
Soon-Shiong, P