CTLA-4 and PD-1 Antibodies Expressing Mesothelin-CAR-T Cells for Mesothelin Positive Advanced Solid Tumor

Inclusion Criteria:

1. Patients with relapsed or refractory advanced solid malignancies (diagnosed by histology or cytology detection).
2. Progressive disease and no response after at least second-line therapy.
3. Gender unlimited, age from 18 years to 80 years.
4. Life expectancy ≥3 months.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
6. Adequate venous access for peripheral blood mononuclear cell (PBMC) apheresis, and no other contraindications.
7. Immunohistochemistry (IHC) score of mesothelin on tumor tissue ≥1+.
8. Adequate bone marrow function, hepatic function and renal function (withhin 7 days before enrollment): white blood cell (WBC)≥3.0×10\^9/L; platelet≥100×10\^9/L; hemoglobin ≥90 g/L; lymphocyte ≥0.7×10\^9/L; total bilirubin ≤2 times the upper limit of the normal value; alanine aminotransferase and aspartate transaminase(ALT and AST) ≤2.5 times the upper limit of the normal value; serum creatinine ≤1.5 times the upper limit of the normal value.
9. There is no other treatments (chemotherapy, radiotherapy, etc.) within four weeks before enrollment.
10. There is at least one measurable tumor lesion.
11. Patients have adequate ability to understand, sign informed consents and take part in the clinical research voluntarily.
12. Female patients in child bearing period must have evidence of negative pregnancy test, and agree to take effective contraceptive measures until 4 months after cells infusion.

Exclusion Criteria:

1. Patients with two or more kinds of tumors.
2. Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
3. Patients with seropositive reponse of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
4. Patients with active rheumatic diseases, organ transplantation and other diseases affecting the immune system seriously.
5. Patients with severe heart and lung dysfunction.
6. Patients with severe chronic diseases of kidney, liver and other important organs.
7. Patients with any other illnesse that the investigators consider it will may affect the patient's treatments, follow-up or assessment, including any uncontrolled clinically significant neurological or psychiatric disorders, immunoregulatory diseases, metabolic diseases, infectious diseases and so on.
8. Patients who take part in clinical trials of other drugs or biological therapy at present or within 30 days before enrollment.
9. Patients who need long-term use of immunosuppressive drugs or patients who are undergoing treatment for autoimmune diseases.
10. Patients who must use glucocorticoid for a long time.
11. Women patients in gestation period or suckling period.