Intervention of Bladder Cancer by CAR-T

• 4SCAR-PSMA (Genetic): PSMA-specific 4th Generation CART
• 4SCAR-FRa (Genetic): FRa-specific 4th Generation CART

Primary outcomes

• Overall Survival rate after receiving 4SCART infusion [1 year]: to determine the efficacy of 4SCAR T cells
• Using CTCAE 4 standard to evaluate the level of adverse events after receiving 4SCART infusion [3 months]: to evaluate the level of adverse events with CTCAE 4

Secondary outcomes

• The expansion and persistence of 4SCAR T cells [1 year]: The investigators will monitor the expansion and functional persistence of 4SCAR T cells in the peripheral blood of patients and the correlation with antitumor effects
• Immune responses after infusions [3 months]: assessment of cytokine profile

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

1. Histologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra)
2. Representative tumor specimens as specified by the protocol
3. Adequate hematologic and end organ function
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Life expectancy greater than or equal to (>/=) 12 weeks
6. Measurable disease, as defined by RECIST v1.1

Exclusion Criteria:

1. Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
2. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
3. Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
4. Leptomeningeal disease
5. Malignancies other than UBC within 5 years prior to Cycle 1, Day 1
6. Pregnant and lactating women
7. Significant cardiovascular disease
8. Severe infections within 4 weeks prior to infusion
9. Major surgical procedure other than for diagnosis within 4 weeks
10. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
11. History of autoimmune disease
12. Prior allogeneic stem cell or solid organ transplant
13. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
14. Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis

• Lung-Ji Chang, PhD, Principal investigator, Shenzhen Geno-Immune Medical Institute