BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in r/r B-ALL

Inclusion Criteria: 1. Age 18-70 (inclusive),gender unrestricted. 2. Patient with r/r CD19+ B-ALL, as per guidelines (NCCN, 2019) * morphologically confirmed with ≥ 5% leukaemic blasts in the bonemarrow; * or presenting a quantifiable MRD load of 1x10\^-3 , assessed by multiparameter flow cytometry and/or quantitative polymerase chain reaction, at the end of the last induction treatment. * who has exhausted alternative treatment options. Relapsed disease is defined as: * second or subsequent bone marrow relapse or, * any bone marrow relapse after allogenic hematopoiesis stem cell transplant (allo-HSCT). Refractory disease is defined by not achieving an initial complete response (CR) after 2 cycles of a standard chemotherapy regimen (primary refractory). Subjects who were refractory to subsequent chemotherapy regimens after an initial remission were considered chemorefractory. 3. Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for hematological toxicities and clinically non-significant toxicities such as alopecia). 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 5. Adequate renal, hepatic, pulmonary and cardiac function defined as: * Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min. * Serum alanine aminotransferase / aspartate aminotransferase (ALT/AST) ≤ 3×ULN; Total bilirubin ≤ 1.5×ULN. * Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings. * Coagulation Function: International Normalized Ratio (INR) ≤ 1.5 ×ULN, and Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN .• Baseline oxygen saturation \>91% on room air. 6. Subjects of both genders who are willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential). 7. Voluntarily participate in this clinical trial and sign an informed consent form. Exclusion Criteria: 1. Expected survival time \< 3 months per Principal Investigator's opinion. 2. 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 \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\]. 3. Prior CD19 targeted therapy 4. Prior CAR-T therapy or other genetically modified T cell therapy. 5. Active central nervous system (CNS) leukaemia (CNS-3). 6. B-ALL with clinically suspected extra-medullary involvement. 7. Burkitt cell (L3 ALL) or mixed lineage acute leukaemia. 8. Clinically active significant CNS dysfunction * History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement. * Known history of irreversible severe neurological toxicity related to previous antileukaemic treatment leading to organic central nervous system lesions. * Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) before Inclusion. 9. Use of previous anti-leukemic therapy within 5 half-lives prior to CAR19TIF cells administration; participation in non-interventional registries or epidemiological studies is allowed. 10. History of severe, immediate hypersensitivity reaction attributed to lymphodepletion drugs or any component of CAR19TIF cells. 11. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. 12. Uncontrolled or active infectious diseases, such as human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B or C, epstein-barr virus (EBV), and cytomegalovirus (CMV) infection. 13. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement. 14. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment. 15. Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome). 16. Primary immunodeficiency. 17. History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years. 18. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months of enrollment. 19. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment. 20. Vaccine ≤ 6 weeks prior to planned start of conditioning regimen. 21. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.