PD-1 Antibody Expressing CAR T Cells for Mesothelin Positive Advanced Malignancies

• 1. Relapsed or refractory advanced solid malignancies.
• 2. Progressive disease and no response to current therapy.
• 3. Patients must have previously received at least one standard therapy for their cancer (if available) and have been either non-responders (progressive disease) or have recurred. And patients are willing to attend the clinical trial.
• 4. Gender unlimited, age from 18 years to 80 years.
• 5. Life expectancy≥6 months.
• 6. ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
• 7. Adequate venous access for apheresis, and no other contraindications for leukapheresis ; Peripheral venous access ；no contraindication of lymphocyte separation.
• 8. IHC( immuno-histochemistry) result of tumor tissue： mesothelin positive for ：frequency≥2，intensity≥2 +. The percentage of tumor cell nuclei stained (0, no staining; 1, ≤10%; 2, 10-50% and 3, >50%) and the staining intensity (ranging from 0 to 3+).
• 9. Adequate hepatic function, renal function and bone marrow function：WBC≥3.0×109/L,PLT≥60×109/L,HGB≥85g/L,LY≥0.7×109/L; Alanine aminotransferase/Aspartate transaminase(ALT/AST) 2.5 times the upper limit of the normal value, total bilirubin(TBiL) 1times the upper limit of the normal value, Serum creatinine1.5 times the upper limit of the normal value.
• 10. Willing and able to understand and sign the Informed Consent Document.
• 11. Women of child-bearing age must have evidence of negative pregnancy test. Patients must be willing to practice birth control during and for four months following treatment.

Exclusion Criteria:

• 1. Life expectancy6 months.
• 2. Patients with uncontrolled active infection will be excluded.
• 3. Patients with severe heart and lung dysfunction; uncontrolled hypertension, unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded; aberrant pulmonary function testing: with a forced expiratory volume (FEV) of \<30%(predicted), diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) \<30% and oxyhemoglobin saturation90% will be excluded.
• 4. Patients with severe liver and kidney dysfunction or chronic diseases of important organs will be excluded.
• 5. Patients with active autoimmune disease requiring immunosuppressive therapy will be excluded.
• 6. Patients requiring corticosteroids (other than inhaled) will be excluded.
• 7. Patients with other severe diseases or situations improper for the research will be excluded, including neurologic disease, mental disease, immune disease, metabolic disease, and contagious disease.
• 8. Pregnant and/or lactating women will be excluded.
• 9. Patients who have had other bio-therapy in the past 4 weeks.
• 10. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.
• 11. Patients with the subject suffering disease affects the understanding of informed consent or complying with study protocol will be excluded.