Valuation of the Safety and Efficacy of Combination of Cryoablation and Dendric Cell/Cytokine-induced Killers Cells Treatment for Advanced Liver Cancers

The treatment of liver cancer needs integrated medical strategies, including surgery, chemotherapy, target therapy, radiotherapy, and immunotherapy. According to the patient's condition to develop a personalized and best treatment plan. Cryoablation can produce osmotic shock through repeated freeze-thaw to cause tumor cell necrosis, and release tumor antigens to activate anti-tumor immune responses. Immune cell therapy is an emerging field across cancer types in current cancer treatment. This study desired to combine cryotherapy and cellular immunotherapy to achieve the effect of tumor control. In recent years, cancer treatment studies have showed that cryoablation combined with immune cell therapy can play a good auxiliary effect and improve the cancer treatment efficacy significantly. This trial study is a single center, single-arm, non-blind open-label human clinical trial. To explore the therapeutic effect and safety of cryoablation combined with autologous DC-CIK (through hepatic artery infusion, HAI) for patients with advanced liver cancers. The DC-CIK biologics are provided by BOHUI Biotech company. Their core technology (including clinical treatment and cell culture techniques) was transferred from Dr. Hasumi who is a Japanese clinician and this technical founder.

Sex

All

Minimum age

20 Years

Maximum age

80 Years

Inclusion Criteria:

1. Patients aged between 20 and 80 years old.
2. Patients with advanced stage hepatocellular carcinoma or advanced stage hepatic metastasis derived from extrahepatic primary carcinoma, who are judged as advanced stage by clinical criteria (The Eighth Edition AJCC Cancer Staging Manual) through pathology and imaging reports.
3. Patients who have been evaluated by a physician for benefits and risks and are no longer considered suitable for previous third-line therapies will be included in this trial.
4. There is at least one target lesion larger than 1.0 cm that can be measured by MRI or CT and is appropriately located for cryoablation by imaging.
5. Child-Pugh class (A or B).
6. Adequate bone marrow function (white blood cell count \> 2x109/L, platelet count \> 5x1010/L).
7. coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of normal
8. renal function: blood creatinine concentration (creatinine) \< 1.5 mg/dL .
9. Karnofsky Performance Status (KPS) score70 -10.
10. maximum tumor diameter ≤ 5 cm
11. number of tumors ≤ 5
12. Survival period greater than 3 months as predicted by the physician.

Exclusion Criteria:

1. Tumor size \>5 cm in diameter or tumor number \>5.
2. not suitable for cytarabine or cryoablation as determined by the trial physician.
3. Blood screening for any of the following viral infections: human immunodeficiency virus, human T-lymphotropic virus, syphilis, hepatitis B virus, hepatitis C virus, cytomegalovirus IgM antibody positive, etc.
4. Previous treatment prior to screening: Chemotherapy or radiation therapy must be completed before 3 weeks of screening to avoid systemic immune responses interfering with the immune cell therapy. If participating in clinical trials of other biologic agents or immunotherapy, at least 4 weeks of screening is required.
5. Patient is acutely or chronically infected or in acute cytomegalovirus attack at the time of screening.
6. Patients with level 3 hypertension, or patients with severe coronary disease.
7. patients with autoimmune disease.
8. patients who are pregnant, breastfeeding, or unable to use effective contraception.

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