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

• Status: Recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Theory of VAK：

1. Immune cells (T cells for example) of cancer subjects may be domesticated by the tumor microenvironment, and have low efficacy to kill cancer cells. They could be restimulated by virus antigen, and play a powerful tumor killing role while intrapleural to subjects.

2. Releasing of tumor-associated antigen could induce specific anti-tumor immune response.

Preparation of VAK：

1. Separate the immune cells and tumor cells from Malignant Pleural and Peritoneal Effusion.

2. Incubate the immune cells with inactivated viruses and tumor cells.

3. Wash to remove impurities.

4. Intrapleural the immune cells to patients

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sheng Hu
• Collaborator: Wuhan Binhui Biotechnology Co., Ltd.

Criteria

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.