Exploratory Study of Novel MSLN CAR-T Cell Therapy in Patients With MSLN-positive Advanced Refractory Solid Tumors

Inclusion Criteria

• •1. Solid tumors positive for the Mesothelin antigen by Immunohistochemistry/Immunocytochemistry (IHC/ICC); histological diagnosis of malignancy refractory to, or relapsing after standard therapy.
• •2. At least one measurable lesion according to RECIST v1.1.
• •3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• •4. Life expectancy ≥ 3 months.
• •5. Neutrophils ≥ 1.0×10\^9/L; Lymphocytes ≥ 0.5×10\^9/L; Hemoglobin ≥ 80 g/L; Platelets ≥ 75×10\^9/L.
• •6. Adequate hepatic, renal, cardiac and coagulation function defined as:
• •* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); patients with liver metastasis must be ≤ 5 × ULN;
• •* Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with Gilbert's Syndrome must less than 3.0 mg/dL;
• •* Serum creatinine (Cr) ≤ 1.5 × ULN, and creatinine clearance rate (Ccr) ≥ 60 mL/min;
• •* Left ventricular ejection fraction (LVEF) \> 45%;
• •* Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• •8. The toxicities from any prior therapy must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo) according to NCI CTCAE v5.0.
• •9. The washout period of previous treatment:
• •* Cytotoxic chemicals, monoclonal antibodies or immunotherapy should be washed out for at least 4 weeks before leukapheresis; anti-CTLA-4 antibodies should be washed out for at least 6 weeks;
• •* Systemic corticosteroids or other immunosuppressive therapies should be washed out for at least 2 weeks before leukapheresis;
• •* Biologicals or other approved molecular targeted inhibitors should be eluted for at least 1 week or 5 half-lives (whichever is longer) prior to leukapheresis.
• •10. Participants must be able to understand the protocol and be willing to enroll the study, sign the informed consent, and be able to comply with the study and follow-up procedures.