Advanced tumor
Conditions
Interventions
study group:Infusion of anti DR5 CAR-T or NKG2D CAR-T cells
Sponsors
Shenzhen Hospital of Chinese Academy of Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. The patient or their legal guardian voluntarily participates and signs an informed consent form; 2. Male or female patients aged 18-70 years (including 18 and 70 years old); 3. Subjects with DR5/NKG2DLs positive solid tumors confirmed by imaging and histology/cytology, whose target expression is determined to be = 1+, have no standard effective treatment scheme at present, or the standard treatment scheme is invalid, or do not tolerate the standard treatment scheme, such as colorectal cancer, esophageal cancer, gastric cancer, kidney cancer, liver cancer, lung cancer, prostate cancer, pancreatic cancer, breast cancer, thyroid cancer, ovarian cancer, endometrial cancer, cervical cancer For bladder cancer, melanoma, mesothelioma, synovial sarcoma, cholangiocarcinoma, etc., patients voluntarily choose to infuse anti DR5 CAR-T or NKG2D CAR-T cells as the treatment scheme; 4. Have measurable or evaluable lesions; 5. The patient's main tissues and organs are functioning well: Liver function: Child Pugh score<7; Pulmonary function: Indoor oxygen saturation = 95%; Cardiac function: Left ventricular ejection fraction (LVEF) = 40%. 6. The patient did not receive any chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) or other anti-cancer treatments within 4 weeks prior to enrollment, and their previous treatment-related toxicity reactions had recovered to = 1 level at enrollment (excluding low-grade toxicity such as hair loss); 7. The patient's peripheral superficial veins have smooth blood flow, which can meet the intravenous drip demand; 8. White blood cells = 2.5 × 109/L, platelet = 60 × 109/L, hemoglobin = 9.0 g/dL, lymphocytes = 0.4 × 109/L, serum albumin = 30 g/dL, serum lipase and amylase = 1.5 upper limit of normal value (ULN), serum creatinine = 1.5 ULN and endogenous creatinine clearance rate = 40mL/min, ALT and AST = 5 ULN, serum total bilirubin = 2.5 ULN, prothrombin time less than 4 seconds longer than normal; 9. If HBsAg or HBcAb is positive, HBV-DNA<200 IU/mL; HBsAg positive patients need to receive antiviral treatment according to the "The guideline of prevention and treatment for chronic hepatitis B: a 2015 update"; 10. Patients with an ECOG score of<2 or a KPS score of = 70 and an estimated survival time of = 3 months. 11. Adequate venous access for single or intravenous blood collection, and no other contraindications for blood cell separation. 12. There is no known or suspected history of tumor involvement in the central nervous system (CNS).
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant (urine/blood pregnancy test positive) or breastfeeding; 2. Men or women who have planned to conceive within the past year; 3. The patient cannot guarantee effective contraceptive measures (such as condoms or contraceptives) within one year after enrollment; 4. The patient has uncontrollable infectious diseases within 4 weeks before enrollment, such as but not limited to active tuberculosis; 5. The imaging results show that = 50% of the liver is occupied by tumors; Or the tumor size exceeds 25cm; Or based on image analysis, there are cancer thrombi in the portal vein, mesenteric vein, or inferior vena cava; 6. Have a history or current status of hepatic encephalopathy, 7. Abnormal thyroid function = level 3; 8. There are cases of organ failure, such as NYHA heart function level IV, Child Turcotte liver function level C, kidney failure or uremia, respiratory failure symptoms, and brain disability caused by the patient; 9. There are heart diseases that require treatment intervention, or poor control of hypertension (systolic blood pressure>160 mmHg, or diastolic blood pressure>100 mmHg); 10. Has a history of organ transplantation or is currently waiting for organ transplantation, including but not limited to liver transplantation; 11. Positive for serum HCV or HIV or syphilis; Or the presence of HBV/HCV co infection; CMV DNA positive patients; (HCV antibody positive and HCV RNA negative individuals can be selected) 12. Inoculated live attenuated vaccine within 4 weeks before single collection; 13. Suffering from severe autoimmune diseases or immunodeficiency diseases; 14. The patient has an allergic constitution and has access to immunotherapy and related drugs, or ß- Allergic history of lactam antibiotics, or other serious allergic history; Or have a history of severe hypersensitivity to the main therapeutic drugs used in this study, including fludarabine, cyclophosphamide, ifosfamide, contrast agents used during pretreatment, as well as Tozumab and anti infective drugs used to prevent and treat CRS; 15. The patient has participated in clinical trials of chemotherapy, radiotherapy, and immunotherapy within 4 weeks prior to enrollment; 16. Systemic use of glucocorticoids by patients within 4 weeks prior to enrollment (excluding those who use inhaled glucocorticoids); 17. Suffering from mental illness or other central nervous system disease; 18. The patient has substance abuse/addiction; 19. According to the judgment of the researchers, the patient has other unsuitable enrollment situations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Remission rate at 3 months; | — |
Secondary
| Measure | Time frame |
|---|---|
| OS;Adverse events of special concern for CAR-T project;AE;SAE;Remission rates at 6 months and 1 year;FPS;EFS;Characteristics of temporal changes in the amplification level of CAR-T cells in subjects; | — |
Countries
china
Contacts
Public ContactXU SHU
Shenzhen Hospital, University of Chinese Academy of Sciences
Outcome results
None listed