頁籤選單縮合
題 名 | Localization of Salmonella and Albumin-IL-2 to the Tumor Microenvironment Augments Anticancer T Cell Immunity |
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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; | 書刊名 | Journal of Biomedical Science |
卷 期 | 29 2022[民111] |
頁 次 | 頁(57)1-(57)12 |
分類號 | 415.569 |
關鍵詞 | Colon cancer; Albumin; Interleukin‑2; IL‑2; Salmonella; |
語 文 | 英文(English) |
DOI | 10.1186/s12929-022-00841-y |
英文摘要 | Background 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. Methods 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. Results 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. Conclusions 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. |
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