Enhanced Therapeutic Effect By Combination Of Tumor-targeting Salmonella And IL-21in Murine Melanoma Model

As one of the most successful tumor-targeting bacterial, Salmonella has being administrated in pre-clinical experiments fighting against various tumors and facilitates treatment efficiently. Salmonella is prone to hpoxia area which is distributed in many tumors. Tumors were then targeted by salmonella via this area. Salmonella induced innate and adaptive immune in vivo to activate immunocytes to resist tumor. Subsequent research revealed limit effect of salmonella itself to treat cancer. Salmonella inhibits tumor growth and facilitate survival in limited ranges, instead of kill tumor efficiently. The advantage of tumor-targeting promotes salmonella to be a useful tool to treat cancer. Researchers applied it to be gene therapy vector to transport anti-tumor gene to tumor position. These strategies shed new light on therapeutic effectiveness of bacterial immensely.Interleukin-21(IL-21) was discovered in this century belongs to γ-Chain cytokine family and its critical regulatory roles in immune system was revealed in the past10years. IL-21promotes proliferation, development and differentiation of B and T immunocytes. Furthermore, it activates CD8+T and NK cells efficiently to augment their cytotoxic effects. IL-21was used to treat cancer immediately upon revealing its function. Based on its promising data from pre-clinical experiment, IL-21is assessed on clinical trial I and II stage now. The data from clinical trial Ⅰ and Ⅱ suggests A promising future of IL-21. In this paper, we cloned the mouse IL-21into pBLAST vector and verified its expression in cellular and tissular levels. We firstly combined IL-21with salmonella to treat murine melanoma. A great synergy was observed in treating murine melanoma with salmonella after combined with IL-21. The combination inhibits the growth of tumor and promotes survival efficiently. Further study exhibits IL-21induced CD4, CD8and NK cells infiltration may contribute to the synergy.Taken together, our data proved advanced therapeutic effectiveness of salmonella combined with IL-21, indicative of new light on the cancer treatment by cytokine and bacterial.