MSLN STAR-T Cells in the Treatment of Advanced Malignant Solid Tumors

Inclusion Criteria: 1. Age ≥ 18 years old, ≤ 70 years old, gender is not limited; 2. Advanced malignant solid tumors confirmed by histology or cytology, including malignant mesothelioma (pleura, peritoneum, etc.), pancreatic cancer, ovarian cancer, intrahepatic bile duct cancer, lung cancer, gastric cancer, colorectal cancer, etc.; 3. Patients with advanced malignant solid tumors who have relapsed after systemic therapy, or who cannot tolerate existing therapy, including but not limited to: * Patients with malignant mesothelioma who have failed at least first-line therapy; * Patients with pancreatic cancer who have failed at least first-line therapy; * Patients with gastric cancer who have failed at least second-line therapy in the past; * Patients with ovarian cancer who have previously failed at least second-line platinum-sensitive or platinum-resistant therapy; * Patients with intrahepatic cholangiocarcinoma who have failed at least first-line therapy; * Patients with advanced non-small cell lung cancer (non-squamous cell carcinoma): positive for EGFR, ALK, ROS1, MET and other driver genes, disease progression or intolerance after targeted therapy; negative for EGFR, ALK, ROS1, MET and other driver genes If the subject has disease progression or intolerance after receiving ≥ 1 line of therapy in the past; * Patients with colorectal cancer who have failed at least second-line therapy. 4. Tumor tissue samples are positive for mesothelin (MSLN) (IHC test, positive rate \> 10%); 5. There are measurable target lesions on imaging (according to RECIST1.1) at the time of screening, the long diameter of non-lymph node lesions is ≥1.0cm, or the short diameter of lymph node lesions is ≥1.5cm; 6. ECOG score 0-1 points; 7. Expected survival period ≥ 3 months; 8. Have the conditions to establish a peripheral blood mononuclear cell collection pathway, and have enough cells for STAR-T cell preparation; 9. Has good bone marrow and organ function: * Blood routine: absolute neutrophil count (ANC) ≥1.5×109/L; hemoglobin (Hb) ≥85g/L; platelet count ≥75×109/L; * Blood biochemistry: total bilirubin (TBIL) ≤ 2.5 times the upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN) (for liver metastases) Patients may be ≤5 times ULN); * Serum creatinine (Cr) ≤ 1.5 times the upper limit of normal (ULN); * Coagulation function: International Normalized Ratio (INR), Activated Partial Thrombin Time (APTT) ≤1.5×ULN, patients with liver metastases should be ≤2×ULN; * Pulmonary function: with the lowest level of lung reserve, defined as CTCAE v5.0 ≤ grade 1 dyspnea and end-finger oxygen saturation ≥ 91% in the non-oxygen state. Exclusion Criteria: 1. Those with uncontrolled active infection at the time of screening; those who meet one of the following: Hepatitis B surface antigen (HBsAg) positive and/or hepatitis B e antigen (HBeAg) positive, hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) positive and HBV-DNA copy number greater than the detection limit, hepatitis C antibody (HCV-Ab) positive and HCV-RNA copy number greater than the lower limit of detection, human immunodeficiency virus (HIV) antibody positive, Treponema pallidum (TP-Ab) antibody positive; 2. Patients with or with a history of central nervous system diseases, such as history of epilepsy, stroke, severe brain damage, aphasia, paralysis, etc.; 3. Patients with active brain metastases but who do not need any radiation, surgery or steroid therapy to control metastatic symptoms 1 month before screening can be enrolled; 4. Systemic lupus erythematosus, combined with active or uncontrolled autoimmune diseases (such as Crohns disease, rheumatoid arthritis, autoimmune hemolytic anemia, etc.); 5. Are receiving therapeutic dose or systemic glucocorticoid therapy (prednisone ≥ 20 mg/day or equivalent dose of other corticosteroids); 6. Toxicity or complications caused by previous interventions or treatments have not recovered to CTCAE v5.0 ≤ grade 2 or below (except for hair loss and abnormal values of laboratory tests judged by the investigator); 7. Previously received other genetically modified T cell products (such as MSLN CAR-T or TCR-T cells), or treatment targeting MSLN; 8. Patients who have received any of the following drugs or treatments within the specified time period prior to apheresis: * Received any chemotherapy within 2 weeks or 5 half-lives, whichever is shorter, prior to apheresis; * Received any macromolecule or small molecule targeted therapy such as monoclonal antibody, antibody-drug conjugate (ADC), double antibody, etc. within 4 weeks or 5 half-lives (whichever is shorter) before apheresis; * Received radiotherapy within 6 weeks before apheresis. If the disease progresses in the radiotherapy site, or there are CT and other image-positive lesions in other non-radiotherapy sites, the group is allowed to enter the group; if there are CT and other image-positive lesions in other non-radiotherapy sites, it is allowed to 2 weeks before harvest, radiotherapy is performed on a single lesion; 9. The presence of uncontrolled pleural effusion, pericardial effusion or ascites (ascites is defined as: ascites with positive signs of ascites on physical examination or ascites that needs to be controlled by intervention (only those with ascites shown by imaging without intervention can be included).