Safety and Efficacy Study of Virus Activated Killer Immune Cells (VAK) for Malignant Pleural and Peritoneal Effusion

Inclusion Criteria:

1. Willing to sign informed consent;
2. Pathological confirmed advanced malignant tumor with malignant pleural or peritoneal effusion;
3. Vital signs stable, Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;
4. Age ≥ 18 years old, gender unlimited;
5. Expected survival period more than 3 months;
6. Subjects agree to take effective contraceptive measures at the time of enrollment and within 4 months after enrollment. The pregnancy test of female patients must be negative;
7. Sufficient bone marrow, liver and kidney functions. Laboratory tests within 7 days before the first drug use meet the following requirements:

   * Coagulation function: APTT ≤ 1.5 × ULN, while INR or PT ≤ 1.5 × ULN (not receiving anticoagulant therapy); ② Blood routine examination: Hgb ≥ 80g / L, WBC \> 3 × 10\^9/L、NEU≥1.0 × 10\^9/L、PLT≥80 × 10\^9/L;
   * Liver function: total bilirubin ≤ 1.5 times the upper limit of normal value (ULN); AST and alt ≤ 2.5 times ULN (if abnormal liver function is mainly caused by tumor infiltration, it can be ≤ 5 times ULN; alkaline phosphatase ≤ 2.5 times ULN; ④ Renal function: bun and Cr ≤ 1.5 times ULN, creatinine clearance ≥ 40ml / min (calculated by Cockcroft Gault formula).

Exclusion Criteria:

1. Subjects requiring emergency treatment due to intestinal obstruction or vascular compression;
2. Subjects with active hemolytic anemia;
3. Subjects with active central nervous system metastases were excluded, except those with brain metastases or asymptomatic cancer cells found in cerebrospinal fluid;
4. Pregnant or lactating female;
5. Systemic active infection, serious coagulation disorder or serious heart, respiratory and immune system diseases;
6. Congenital or acquired immune function defects (such as HIV infection), hepatitis B infection (HBV-DNA ≥ 10 \^ 4 / ml), hepatitis C infection (HCV antibody and HCV RNA positive);
7. Subjects who had serious infection within 4 weeks before the first medication were excluded, including but not limited to infectious complications, bacteremia and severe pneumonia requiring hospitalization;
8. Subjects with active autoimmune diseases or a history of autoimmune diseases that may recur, but the following are not excluded:

   * Type 1 diabetes
   * Hypothyroidism (if controlled by hormone replacement therapy only)
   * Controlled celiac disease ④ Skin diseases without systemic treatment (such as vitiligo, psoriasis, alopecia) ⑤ Any other disease that does not recur without external triggers.
9. Those who had severe hypersensitivity to the drugs used in this protocol in the past;
10. Subjects who are ready for or have previously received tissue / organ transplantation;
11. Subjects with large pericardial effusion were excluded;
12. Exclude those who have suffered from other malignant tumors within 2 years, except for cervical carcinoma in situ, low-risk gastrointestinal stromal tumor, skin basal cell carcinoma, skin squamous cell carcinoma, thyroid papillary carcinoma and breast ductal carcinoma in situ that have been effectively removed;
13. Exclude subjects who have been vaccinated or will be vaccinated with live vaccine within 4 weeks before the first administration;
14. Other circumstances that the investigator considers inappropriate for clinical trials.