A human recombinant IL-7/HGF beta hybrid cytokine enhances antitumor immunity in mice

作者：Han Feng; Hu Rong; Su Min; Yu Yanni^*; Yang Hua^*; Lai Laijun^*

来源：American Journal of Cancer Research, 2017, 7(8): 1714-1723.

• Tumor immunotherapy
• cytokines
• mice
• T cells
• dendritic cells
• metastasis

We purified a hybrid cytokine that contains interleukin-7 (IL-7) and the beta-chain of hepatocyte growth factor (HGF beta) from a unique long-term murine bone marrow culture system. We have cloned and expressed the human form of IL-7/HGF beta in which the IL-7 and HGF beta genes are connected by a flexible linker to produce a single-chain recombinant human IL-7/HGF beta protein (hrIL-7/HGF beta). To determine whether hrIL-7/HGF beta has antitumor activity, we injected this hybrid cytokine into melanoma and colon cancer animal models, and then assessed the local tumor growth and tumor metastasis. We show here that in vivo administration of hrIL-7/HGF beta significantly inhibited the growth and metastasis of malignant melanoma and colon cancer in mice. The antitumor activity was involved in a marked increase in the number of tumor-infiltrating CD4(+) and CD8(+) T cells and activated dendritic cells. The immunological mechanism by which hrIL-7/HGF beta inhibits tumor growth was confirmed by its inability to inhibit tumor growth in vitro and in immunodeficient mice. Furthermore, immune cells from hrIL-7/HGF beta-treated cancer-bearing mice can be adoptively transferred into naive mice to resist same tumor cell challenge. Therefore, hrIL-7/HGF beta has potential applications in the treatment of cancer patients.

• 出版日期2017