CD19/CD22 CAR-T Consolidation in R/R Aggressive B-Cell Lymphoma After Second-Line Therapy

The purpose of this study is to determine the efficacy and safety of CD22/CD19-targeted CAR-T cell immunotherapy as consolidation therapy after second-line treatment in patients with high-risk aggressive B-cell lymphoma.

Inclusion Criteria: * 1\. With the patient's consent and signed informed consent form, willing and able to comply with the planned visits, research treatments, laboratory tests, and other experimental procedures; 2. CD19 and/or CD22-positive large B-cell lymphoma (LBCL) diagnosed by cytology or histology according to WHO 2016 criteria, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), etc., whose disease has achieved complete response (CR) after induction treatment with a standard second-line chemotherapy regimen and who are within 3 months from the time of CR. 3\. The possible high-risk factors for the patient's onset of the disease are as follows: 1) FISH confirmed high-grade B-cell lymphoma with double or triple strikes, accompanied by MYC and BCL2 and/or BCL6 rearrangements; 2) Advanced B-cell lymphoma with 11q abnormalities/Burkitt like lymphoma with 11q abnormalities; 3) The International Prognostic Index (IPI) at the time of initial diagnosis is 2-5 points; The Age Adjusted International Prognostic Index (aaIPI) is 2-3 points; The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score ranges from 4-8 points in the United States; 4) Immunohistochemical CD5 positivity; 5) Immunohistochemistry suggests dual expression of MYC and BCL-2 (recommended dual expression threshold is MYC ≥ 40%, BCL2 ≥ 50%); 6) Gene sequencing shows TP53 mutation; 7) The second-generation sequencing (NGS) suggests molecular typing as MCD subtype and N1 subtype; 4. Age range from 18 to 85 years old, male or female; 5. Subjects with physical fitness status scores ranging from 0 to 2 in the Eastern Cooperative Oncology Group (ECOG) in the United States; 6. Expected survival period from the date of signing the informed consent form is greater than 3 months; 7. HGB ≥ 60g/L; 8. The absolute value of neutrophils in peripheral blood is ≥ 1000/μl, and the platelet count is ≥ 45000/μl; 9. Liver and kidney function, as well as heart and lung function, meet the following requirements: 1) Total bilirubin (TBIL) ≤ 1.5 times the upper limits of normal (ULN), except for subjects with Gilbert's syndrome; 2) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN; 3) Serum Creatinine (Cr) ≤ 1.5 times ULN or Creatinine Clearance Rate (CCr) ≥ 60mL/min, estimated based on the Cockcroft Gault formula; 4) The left ventricular ejection fraction (LVEF) of the heart is ≥ 50%. Echocardiography (ECHO) confirms no pericardial effusion and no clinically significant arrhythmia; 5) Baseline transcutaneous oxygen saturation under indoor ventilation\>92%; 6) No clinically significant pleural effusion; 10. Participants with pregnancy plans must agree to take contraceptive measures for a continuous period of 6 months from before enrollment in the study until the end of the study; If the subject is pregnant or suspected of being pregnant, the researcher should be notified immediately. 11.Patients who are not eligible for hematopoietic stem cell transplantation (HSCT) or who refuse HSCT. Exclusion Criteria: * 1\. Have received any form of chimeric antigen receptor cell therapy or other genetically modified T cell therapy; 2. Has a history of severe immediate hypersensitivity reactions to aminoglycoside antibiotics and other essential medications; 3. Known history of human immunodeficiency virus (HIV) infection or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics (active HBV infection is defined as: a. HBV DNA quantification ≥ 2000 IU/ml; b. ALT ≥ 2 times the normal upper limit value; c. Exclude hepatitis caused by the disease itself, medication, or other reasons; All three conditions must be met simultaneously. If a patient is diagnosed with active HBV infection at the time of initial diagnosis and becomes non active HBV infection after anti HBV treatment, they can be included in this study under the premise of sufficient anti HBV treatment; 4. Non hematological tumors (such as lymphoma) associated liver and kidney dysfunction: ALT\>3 times the upper limit of normal, AST\>3 times the upper limit of normal, TBIL\>2 times the upper limit of normal, serum creatinine clearance rate\