Clinical Research of CD19 Targeted CAR-T Cell in Relapsed/Refractory B Cell Lymphoma

Inclusion Criteria: 1. The patient or his/her guardian agrees to participate in the clinical trial and signs the ICF, indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study; 2. Age ≥18 years old, gender unlimited; 3. Confirmed cytological or histological diagnosis of B-cell non-Hodgkin lymphoma according to WHO 2017 criteria, including the following pathological types: 1. Diffuse large B-cell lymphoma: including non-specific type (DLBCL, NOS), chronic inflammatory associated DLBCL, primary cutaneous DLBCL (leg type), EBV-positive DLBCL (NOS); 2. High-grade B-cell lymphomas (including NOS and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements); 3. Primary mediastinal large B-cell lymphoma; 4. Rich T/ histiocytic large B-cell lymphoma; 5. Transformed DLBCL (e.g., transformed DLBCL of follicular lymphoma, chronic lymphocytic leukemia/small B lymphocytic lymphoma, marginal zone lymphoma, etc.); 6. Grade 3b follicular lymphoma (FL3b); 4. Have received adequate treatment with CD20 monoclonal antibody and anthracyclines in the past (except for those who are negative for CD20 and anthracyclines, or who are unable to tolerate or adapt to CD20 monoclonal antibody therapy or have other conditions in which the use of CD20 monoclonal antibody is not considered appropriate by the investigators), For those who are allergic to CD20 monoclonal antibody, or have intolerable serious adverse reactions after use, or have active infections and serious cardiovascular problems, etc.), the definition of relapse or refractory is met during screening: 1. Recurrence: recurrence of disease progression or recurrence after achieving CR with standard treatment; 2. Difficult to treat: The best curative effect after at least 4 courses of first-line treatment/at least 2 courses of end-line treatment (2 lines and more) is disease stabilization (SD), and the SD maintenance time after the last dose is not more than 6 months; Or the best response to the last treatment was disease progression (PD); 3. No remission, disease progression or recurrence after autologous hematopoietic stem cell transplantation; 4. Patients with transformational lymphoma who received chemotherapy prior to transformation and did not go into remission, disease progression, or relapse after salvage therapy after transformation. 5. Immunohistochemical or flow cytometry results showed positive CD19 expression; 6. ECOG 0 \~ 1 points; 7. The expected survival time is 12 weeks or more; 8. According to the 2014 edition of Lugano standard, there is at least one two-dimensional measurable lesion as the evaluation basis: for intranodular lesion, it is defined as: long diameter \>1.5cm; For extranodal lesions, the length diameter should be \>1.0cm; 9. The functions of important organs are basically normal: 1. Cardiac function: cardiac echocardiography suggests cardiac ejection fraction ≥50%; 2. Serum creatinine ≤2.0× ULN, or creatinine clearance ≥60ml/min (CockcroftGault formula); 3. ALT and AST≤3.0×ULN (≤5.0×ULN for patients with liver invasion); 4. Total bilirubin ≤1.5 ×ULN (total bilirubin ≤3.0 ×ULN in Gilbert syndrome); 5. Blood oxygen saturation ≥92% in non-oxygen state; 6. Blood routine: neutrophils ≥1.0×109/L, platelets ≥75×109/L, hemoglobin ≥80g/L (with bone marrow invasion, neutrophils ≥0.5×109/L, platelets ≥50×109/L). 10. No serious mental disorders; 11. The venous access required for collection can be established, and mononuclear cell collection can be performed according to the judgment of the researcher, and there are no contraindications for other cell collection; 12. Women of childbearing age who have had a negative pregnancy test and all subjects agree to use a reliable and effective contraceptive method for contraception (excluding safe period contraception) for 1 year from signing the informed consent to receiving the infusion of MC-1-50 cells. Including but not limited to: abstinence, can inhibit ovulation implantable progesterone contraceptive; Intrauterine device (IUD); Intrauterine hormone release system; Spousal vasectomy; Combined hormonal contraceptives (oral, vaginal, and transdermal) that inhibit ovulation; Progesterone contraceptives (oral or injectable) that inhibit ovulation; Male subjects who have sex with a fertile female must consent to the use of a barrier method of contraception (e.g., condom plus spermicidal foam/gel/film/emulsion/suppository). At the same time, the subject should promise not to donate eggs (egg cells, oocytes) or sperm for assisted reproduction within 1 year after the cell infusion. Exclusion Criteria: 1. Secondary CNS lymphoma was allowed to be included, except those with active CNS invasion or symptoms of CNS involvement or primary CNS lymphoma at the time of screening; 2. Patients who have received CAR-T therapy or other gene-modified cell therapy before screening; 3. Received allogeneic hematopoietic stem cell transplantation (allo-HSCT) before screening; 4. Received the following anti-tumor therapy before cell infusion: received chemotherapy, targeted therapy and other drug treatment (preconditioning) within 14 days or at least 5 half-lives (whichever is longer) Except for therapy and sheath chemotherapy for CNS lymphoma, which should be stopped 1 week before cell infusion); Received radiation within 14 days; 5. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA detection greater than the normal range; Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA detection greater than the normal range; Positive for human immunodeficiency virus (HIV) antibodies; Syphilis positive; Cytomegalovirus (CMV) DNA test positive; 6. Have any of the following heart conditions: 1. New York Heart Association (NYHA) Stage III or IV congestive heart failure;