- 作者: Yu-Jui Kung, Brandon Lam, Ssu-Hsueh Tseng, Alana MacDonald, Hsin-Fang Tu, Suyang Wang, John Lin, Ya Chea Tsai, T. C. Wu & Chien-Fu Hung
- 作者服務機構: 1.Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA 2.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA 3.Graduate Program in Immunology, Johns Hopkins School of Medicine, Baltimore, MD, USA 4.Stanford University School of Medicine, Stanford, CA, USA
- 中文摘要:
- 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. - 中文關鍵字:
- 英文關鍵字: Colon cancer, Albumin, Interleukin-2 (IL-2), Salmonella