Study of Activated CIK Armed With Bispecific Antibody for Advanced Liver Cancer

Inclusion Criteria:

1. 18-75 years old;
2. The patient is diagnosed as advanced liver cancer,MUC1/CEA/EpCAM/GPC3 is positive;
3. There is at least one tumor should be measured,and length≥10mm of focus not at lymph node or length≥10mm of focus at lymph node;
4. C interval of BCLC;
5. The patient can't tolerate system(systemic chemotherapy/molecular targeted therapy) or local therapies;
6. Child-Pugh Score ≤7;
7. If the patient received adjuvant chemotherapy after local treatment,the time should be more than 4 weeks after the end of chemotherapy, and disease progression or metastasis patients can also assigned into the group;
8. The time of surgical treatment≥ 3 months ;At the end of the intervention, radiotherapy and the end of the ablation time is more than 4 weeks;
9. The expected survival time ≥4 months；
10. The patient did not took any antitumor drugs within two weeks(any antitumor drugs, Chinese patent medicine including Delisheng injection, Kanglaite injection, Aidi injection, huaier granule and Ganfule Pian);
11. ECOG Score ≤1；
12. HBV DNA\<10\^4copies/ml（2000IU/ml);
13. Serum albumin≥28g/L,ALT and AST≤5.0×ULN,TBIL≤1.5×ULN, electrolyte is normal, proteinuria = 0 \~ 1 +, serum creatinine≤1.5 x ULN;
14. Tests of blood,liver and kidney should meet the following criteria:WBC≥3×10\^9/L,NEUT≥1×10\^9/L,Hemoglobin ≥90 g/L,ANC≥1.5×109/L,PLT≥50×10\^9/L;
15. No serious disease are conflicts with the solution(such as autoimmune disease,immunodeficiency,orgen transplantation);
16. Sign the informed consent;

Exclusion Criteria:

1. Severe cirrhosis, medium or above ascites;
2. Cancer embolus in the main portal vein and first branch, Hepatic duct and first branch, hepatic vein, inferior vena cava;;
3. Patients of T cell lymphoma、myeloma,and patients are using immunosuppressant;
4. Systemic autoimmune diseases, allergic constitution or immunocompromised patients.
5. Patients of chronic diseases need immune stimulant or hormone therapy ;
6. Patients of active bleeding or coagulant function abnormality（PT\>16s、APTT\>43s、TT\>21s、INR≥2）,and patients of bleeding tendency or are receiving thrombolysis and anticoagulation and antiplatelet therapy;
7. Women who is pregnant or during breast feeding or plan to pregnant in 2 years,and not willing to contraception during the test;
8. Any significant clinical and laboratory abnormalities, the researchers think that affect the safety, such as: incontrollable active infection (\> NCI - CTC AE v4.0 standard level 2), uncontrolled diabetes (\> level 2 of NCI - CTC AE v4.0 ), hypertension and can't be controlled by two or less hypotensor(systolic pressure \< 140 mmHg, diastolic pressure \< 90 mmHg), grade II or above peripheral neuropathy (NCI CTC AE v4.0), grade II or above congestive heart failure (NCI CTC AE v4.0), myocardial infarction in 6 month, thyroid dysfunction (\> level 2 of NCI - CTC AE v4.0), etc;
9. Patients with brain、dura mater metastases or history of psychogeny;
10. Gastrointestinal bleeding in the past six months or have clear gastrointestinal bleeding tendency,such as: patients of local active ulcerative lesions, defecate occult blood + + above shall not enter into group; defecate occult blood + depend on gastroscopy;
11. Patients with severe stomach/esophageal varices and need for intervention treatment;
12. Patients with abdominal fistula, gastrointestinal perforation or abdominal abscess within 4 weeks before the first treatment;
13. Patients with glomenrular filtration rate abnormal obviously(The endogenous creatinine clearance \< 60 ml/min or serum creatinine \> 1.5 x ULN);
14. Positive for HIV antibody;
15. Patients who are allergic to computed tomography (CT) and magnetic resonance imaging (MRI) contrast agents at the same time, can't imaging assay;
16. Patients accepted any experimental drugs or pilot medical apparatus and instruments in the past 4 weeks of first treatment;
17. Other reasons the researchers think not suitable.