Clinical Studies Of DC-CIK Cells Were Co-cultured With Transcatheter Hepatic Arterial Chemoembolization For Middle-late Stage Hepatocellular Carcinoma

Transcatheter arterial chemoembolization (TACE) is a minimally invasive technique for the treatment of primary hepatocellular carcinoma. That catheter was selectively inserted into the tumor feeding arteries, anticancer drugs or drug microsphere embolism chemotherapy, then injected into appropriate embolic agent, target artery occlusion, leading to ischemic necrosis of tumor tissue. Because it can significantly increase the local drug concentration, small systemic side effects, can be combined a number of several drugs, such as these advantages make it widely used in the treatment of patients with middle-late stage primary hepatocellular carcinoma can not be surgical resection. But this method also has obvious defects, it is always difficult to make the tumor nourish blood vessels completely embolism, and the immune function of patients decreased after treatment, easily lead to residual tumor recurrence and metastasis.In recent years, with the development of cellular immunology and molecular biology, tumor cell immunotherapy has become to a new treatment method following surgery, radiotherapy, chemotherapy, molecular targeted therapy,.Brought new hope for the treatment of primary hepatocellular carcinoma with low immunogenicity. At present, more research and application in the aspect of cell immunotherapy:dendritic cells (DC), cytokine-induced killer cells (CIK), and dentritic cell/cytokine-induced killer cells(DC-CIK). DC is professional antigen presenting cell (APC) and can uptake, processing and presenting antigens, and is considered to be the only activation of resting T cells and antigen presenting cells in our body, initiate T cell mediated immune responses, play a key role in the anti tumor immune response. CIK is a group of heterogeneous cell that composed of a variety of cells, These cells have a strong anti-tumor activity of T lymphocytes and the characteristic of natural killer cells (NK) non major histocompatibility antigens (MHC) restricted to kill the tumor. Studies have shown that combined highly efficient killing activity CIK cells with powerful tumor antigen presenting capacity DC treat malignant tumor, can play a synergistic anti-tumor effect, was deemed to be the first choice of adoptive cellular immunotherapy.The study analysis of 62 cases of liver cancer patients after TACE in Jingzhou Central Hospital. Grouping according to whether or not combined with DC-CIK cell immunotherapy. To evaluate the changes of short-term efficacy, quality of life, AFP, and survival rate etc of TACE combined with DC-CIK cell immunotherapy in the treatment of primary hepatocellular carcinoma, To provide evidence for further clinical application of DC-CIK cell immunotherapy.Objective:To investigate the effects of TACE combined with autologous DC-CIK cell biological therapy and TACE alone in the treatment of middle-late stage primary hepatocellular carcinoma in short-term efficacy, quality of life, AFP, survival rate and other aspects.Methods:1. Select 62 patients with middle-late stage primary hepatocellular carcinoma underwent TACE in the department of digestive internal medicine, oncology and interventional from January 2014 to March 2015 in the Jingzhou Central Hospital.2. According to whether or not combined with DC-CIK cell biological treatment after TACE is divided into 2 groups, including the study group (TACE+DC-CIK treatment) 30 cases, the control group (only TACE treatment) 32 cases.3. The study group collected peripheral blood mononuclear cells, then isolated DC、CIK cell, packed 2 bottles of culture, After seven days to collect DC cells and CIK cells according to the ratio of co-culture of 1:10. After 12 days, the DC-CIK cells were harvested, Bacteria, mycoplasma, fungi and endotoxin were detected by sampling, All of the samples were qualified for three times.4. Two groups of patients after treatment evaluation of short-term efficacy, quality of life, AFP, safety, survival rate and other changes.Results:1. short-term effects:after half a year, the study group, control group of ORR respectively 60.0%(17/30),28.1% (9/32), by comparative the study group was significantly higher than that of the control group (χ2=5.180、P=0.022), a statistically significant; study group and the control group of DCR were90.0% (27/30) and 71.9% (23/32), were compared between the two groups no significant difference (χ2=3.259、 P=0.071).2. Quality of life:after treatment, most patients have increased physical strength. The effective rate of KPS in the study group was significantly higher than that in the control group (93.3% vs68.8%, P=0.014<0.05).3. AFP:1 weeks before treatment and 4 weeks after treatment, the peripheral blood samples were collected and detected AFP. After treatment, the study group, control group AFP were decreased, the rate of decline was 87.5% (14/16),52.9% (9/17). the rate of decline of the study group was higher than the control group, the comparison was statistically significant (P=0.031<0.05).4. Safety of DC-CIK cells:30 patients after treated with DC-CIK cells 3 cases of patients had a fever (T<38.5℃), were self cooling, no chills, high fever and rash. All cells with cell therapy were 1 months before treatment and after 1 months of monitoring blood, biochemical examination, there were no bone marrow suppression and liver or renal function damage.5.Survival rate:62 patients were followed up for 12 months after treatment. Study group for 6 months and 12 months survival rate were 96.7% (29/30),80.0% (24/30) and the control group for 6 months and 12 months survival rate were 81.2% (26/32),56.2%(18/32); 6 months survival rate isχ2=3.674, P=0.055, the two groups had no obvious abnormalities;12 months survival rate isχ2=3.997、P=0.046, P<0.05, the difference was statistically significant.Conclusion:The cultured autologous DC-CIK cells combined with transcatheter hepatic arterial chemoembolization in the treatment of middle-late stage hepatocellular carcinoma is good, significantly reduced tumor size and AFP lever, improve the patient’s immune function, and reduce adverse reactions. TACE combined with autologous DC-CIK cells in the treatment of middle-late stage hepatocellular carcinoma has good curative effect, significantly improve the short-term curative effect, improve the quality of life of patients, significantly reduce the level of AFP, security is good, no obvious adverse reactions.