CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors

• Choose appropriate advanced cancer patients with Claudin6, GPC3, Mesothelin, or AXL expression, with written consent for the study;
• Perform PBMCs apheresis from the patient and isolate NK cells, transfect the NK cells with Claudin6, GPC3, Mesothelin, or AXL targeting CAR, amplify the number of transfected NK cells as needed, test the quality and killing activity of the Claudin6, GPC3, Mesothelin, or AXL-CAR-NK cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
• To enhance the killing capability, some CAR-NK cells are genetically engineered to express and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Lag3; some CAR-NK cells are combined with Cannabidiol(CBD) or Nicotinamide adenine dinucleotide (NAD);
• Evaluate the clinical results as needed.
• Will also perform the similar clinical trial on different cancer types with Claudin6, GPC3, Mesothelin, or AXL expression.

Inclusion criteria

• patients with advanced ovarian cancer or other cancers with expression of claudin6.
• Life expectancy >12 weeks
• Adequate heart,lung,liver,kidney function
• Available autologous transduced NK cells with greater than or equal to 20% expression of Claudin6, GPC3, Mesothelin, or AXL-CAR determined by flow-cytometry and killing of claudin6-positive targets greater than or equal to 20% in cytotoxicity assay
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Exclusion criteria

• Had accepted gene therapy before;
• Tumor size more than 25cm;
• Severe virus infection such as HBV,HCV,HIV,et al
• Known HIV positivity
• History of liver/renal transplantation
• Active infectious disease related to bacteria, virus,fungi,et al
• Other severe diseases that the investigators consider not appropriate;
• Pregnant or lactating women
• Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
• Other conditions that the investigators consider not appropriate. -