CD40 Ligand Expressing MSLN-CAR T Cell Therapy in MSLN Positive Advanced/Metastatic Solid Tumors

In preclinical study, investigators have demonstrated that the newly developed CD40 ligand expressing MSLN-CAR T cells possess more powerful antitumor activity than previously reported CAR-MSLN T cells in animal models. In this clinical trial, at least 9 eligible patients in dose escalation period will be enrolled to receive 3 doses of CD40 ligand expressing MSLN-CAR cell therapy according to the "3+3" principle. In dose expansion period, additional 10 to 21 patients will be enrolled to receive CD40 ligand expressing MSLN-CAR T cell therapy at dose of RP2D.

Inclusion Criteria:1. Age from 18 to 75 years with estimated life expectancy >3 months.2. Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. Mesothelin antigen expression percentage ≥ 10%.3. Have at least one measurable target lesion.4. Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor rebiopsy in the process of this study.5. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity.6. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 at the time of enrollment.7. Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs.8. Previous treatment with anti-PD-1/PD-L1 antibodies are allowed.9. Ability to understand and sign a written informed consent document.10. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug.Exclusion Criteria:1. Active, known or suspected autoimmune diseases.2. Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.3. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.4. History of severe hypersensitive reactions to other monoclonal antibodies.5. History of allergy or intolerance to study drug components.6. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.7. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.8. Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.9. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).10. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.11. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].12. Vaccination within 30 days of study enrollment.13. Active bleeding or known hemorrhagic tendency.14. Subjects with unhealed surgical wounds for more than 30 days.15. Being participating any other trials or withdraw within 4 weeks.