The Therapeutic Role Of IL-15/IL-15RA In Hepatic Metastases Mice

The liver is a vital organ of the body, and responsible for many important functions. The treatment effect on liver cancer and metastasis of liver cancer cells is poor with a high mortality rate, which has serious harm human health. Tumor immune therapy has become one of the important tumor early treatment means, through activating the body's immune system to control the growth of tumors, destroy cancerous cells, obtain anti-tumor immune memory, has become a cancer treatment research hotspot. Among them, interleukin 15 to a variety of interleukin immune cells, such as memory T lymphocytes, natural killer cells, natural killer T cell development, differentiation, activation, proliferation has important effect, however, between interleukin 15 in the body and the short half-life endemic in by way of trans deferred by interleukin 15 receptor alpha subunit, assume this receptor deferred the beta/gamma subunit characteristics and the body use interleukin 15 immune therapy, although which have made some achievements, the effect is not very obvious. Have reports in the literature, use of the preparation of interleukin 15 and interleukin 15 receptor alpha subunit, immune therapy, the compound could make interleukin 15 in the body, maximum significantly enhance activity of a variety of lymphocyte function. In addition, relative to the treatment of interleukin 15, use the complexes in melanoma can the treatment of better results, and expound is enhancing tumor infiltration CD8~+ T lymphocyte function to realize an anti-tumor effect.Liver rich in a lot of immune cells, therefore, liver cancer immunotherapy is an extremely advantageous place. This study explores the interleukin 15 and interleukin 15 receptor alpha subunit, complex in the treatment of liver metastasis model, through the effect of molecular biology method successfully constructed contains interleukin 15 and interleukin 15 receptor alpha subunit, complex genetic plasmid and testing the plasmid constructed in the body to CD8~+T cells and the role of NK cells in mice, using CT26 colorectal cancer cell lines hepatoportal injection successfully established a liver metastases model and through the tail vein high-pressure injection plasmid for immune therapy, and seeks to this model optimal tumor growth doses and analysis of the tumor model lymphocytes apoptosis factor 1 on the expression, the number of regulatory T cells, and the analysis using the complex in cancer prevention and treatment of effect, finally through specific lymphocytes delete experiment to find interleukin 15 mediated the mechanism of immune killer, these studies for interleukin 15 and interleukin 15 receptor alpha subunit, complex clinical treatment in liver cancer and subsequent immune combination therapy research offers important theory basis. Main results are as follows:⑴Success constructing interleukin 15 and interleukin 15 receptor alpha and matrix composite material grain, this building with the plasmid interleukin 15 function, can promote body CD8~+ T cells and NK cell proliferation;⑵CT26 colorectal cancer cells in mice by hepatoportal injection established Balb/c liver metastasis immune therapy mouse models of the best dose for 1×10~5, in the tumor model, CD8, CD4 T lymphocytes, and the number of NK cells with cancer development, meanwhile, CD8 increases CD4 T lymphocyte membrane surface and apoptosis factor1 expression level rise, the number of regulatory T cells will increase;⑶After inject the plasmid of interleukin 15 and interleukin 15 receptorαchain, construct the model of hepatic metastases, this group have no tumor occoured. At the same time, the ratio of CD8/CD4 of this group is obviously improving. So interleukin 15 can effective control the scale of the occurrence of cancer prevention;⑷Through the treatment of liver after the macroscopic observation and weight of statistical analysis, the group of super IL-15 have little tumor while the control group have more. So liver interleukin 15 and interleukin 15 receptor alpha subunit, complex in the treatment of liver metastasis model effect is very good;⑸Specificity delete CD8~+T cells and NK cells, the group of delete CD8~+T cells not prevent tumor while the group of delete NK cells have still little tumor, confirmed mediating NK cells and resistance to liver tumor effect mainly by CD8~+T lymphocytes instead of NK cells.