PSMA-specific CAR-T Cell Therapy

Inclusion Criteria:

1. Patients with tumors have received standard first-line therapy and have been judged tobe non-respectable, metastatic, progressive or recurrent.

2. The expression status of PSMA antigens in the tumor tissue will be determined foreligibility. Positive expression is defined by PMSA antibody staining results based onimmunohistochemistry or flow cytometry analyses.

3. Body weight greater than or equal to 10 kg.

4. Age: ≥1 year and ≤ 75 years of age at the time of enrollment.

5. Life expectancy: at least 8 weeks.

6. Prior Therapy: There is no limit to the number of prior treatment regimens. Any grade 3 or 4non-hematologic toxicity of any previous therapy must have resolved to grade 2 orless.

7. Participant must not have received hematopoietic growth factors for at least 1 weekprior to mononuclear cells collection.

8. At least 7 days must have elapsed since the completion of therapy with a biologicagent, targeted agent, tyrosine kinase inhibitor or a metronomic non-myelosuppressiveregimen.

9. At least 4 weeks must have elapsed since prior therapy that included a monoclonalantibody.

10. At least 1 week since any radiation therapy at the time of study entry.

11. Karnofsky/jansky score of 60% or greater.

12. Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55percent.

13. Pulse Ox greater than or equal to 90% on room air.

14. Liver function: defined as alanine transaminase (ALT) <3x upper limit of normal (ULN),aspartate aminotransferase (AST) <3x ULN; serum bilirubin and alkaline phosphatase <2xULN.

15. Renal function: Patients must have serum creatinine less than 3 times upper limit ofnormal.

16. Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul,Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved bytransfusion).

17. Patients with known bone marrow metastatic disease will be eligible for study as longas they meet hematologic function criteria, and the marrow disease does not havehematologic toxicity.

18. For all patients enrolled in this study, themselves or their parents or legalguardians must sign an informed consent and assent.

Exclusion Criteria:

1. Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.)or major organ dysfunction, or greater than grade 2 hematologic toxicity.

2. Untreatable central nervous system (CNS) metastasis: Patients with previous CNS tumorinvolvement that has been treated and is stable for at least 6 weeks followingcompletion of therapy are eligible.

3. Previous treatment with other genetically engineered PSMA-specific CAR T cells orantibody therapy.

4. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolledinfection.

5. Patients who require systemic corticosteroid or other immunosuppressive therapy.

6. Evidence of tumor potentially causing airway obstruction.

7. Inability to comply with protocol requirements.

8. Insufficient CAR T cells availability.