Novel Bispecific AbTCR (Anti-CD19/CD22)-T Cells in Relapsed or Refractory B-cell Lymphoma

Inclusion Criteria: 1. Age≥ 18 years; 2. Pathologically diagnosed CD19+/CD22+ B-cell lymphoma; 3. Relapsed or refractory after at least two prior lines of therapy; 4. Patient's main organs functioning well: 1. Cardiac function: Left ventricular ejection fraction ≥50%; 2. Liver function: ALT and AST ≤2.5 × upper limit of normal (ULN), total bilirubin ≤2 × ULN; 3. Renal function: Serum creatinine ≤3.0 mg/dL (≤260 μmol/L); 4. Pulmonary function: ≤CTCAE grade 1 dyspnea and Indoor oxygen saturation ≥92%; 5. Adequate bone marrow function as assessed by the investigator to receive lymphodepleting chemotherapy; 5. Adequate vascular access for leukapheresis; 6. Women of childbearing potential (all women physiologically capable of becoming pregnant) must agree to use highly effective contraception for 1 year after AbTCR (anti-CD19/CD22)-T cell infusion, such as copper-containing intrauterine device, hormonal implants, or tubal ligation; male subjects with partners of childbearing potential must agree to use effective barrier contraception for 1 year after AbTCR (anti-CD19/CD22)-T cell infusion; 7. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form. Exclusion Criteria: 1. Lymphoma involving only the central nervous system (CNS), or secondary CNS lymphoma patients judged by the investigator to be at high risk for AbTCR (anti-CD19/CD22)-T cell therapy; 2. History of other malignancies not in complete remission for at least 2 years (the following conditions are exempt from the 2-year restriction: non-melanoma skin cancer, completely resected stage I tumors with low risk of recurrence, treated localized prostate cancer, biopsy-confirmed cervical carcinoma in situ, or PAP smear showing squamous intraepithelial lesion); 3. Any of the following at screening: 1. Positive hepatitis B surface antigen (HBsAg) (regardless of hepatitis B virus DNA copy number); 2. Positive hepatitis B core antibody (HBcAb) with increased hepatitis B virus DNA copy number; 3. Hepatitis C, human immunodeficiency virus (HIV), or syphilis infection; 4. Deep vein thrombosis (DVT) or pulmonary embolism (PE) within 3 months prior to signing informed consent; 5. Ongoing anticoagulant therapy for deep vein thrombosis (DVT) or pulmonary embolism (PE) within 3 months prior to signing informed consent; 6. Uncontrolled systemic fungal, bacterial, viral, or other infection; 7. Acute or chronic graft-versus-host disease (GvHD); 8. History of any of the following cardiovascular diseases within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart disease; 9. History of or current clinically significant CNS disease at screening, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychiatric illness; 10. Pregnant or breastfeeding women. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to starting lymphodepleting chemotherapy; 11. Use of any of the following drugs or treatments within the specified timeframes prior to leukapheresis: 1. Alemtuzumab within 6 months prior to leukapheresis; 2. Cladribine within 3 months prior to leukapheresis; 3. Fludarabine within 3 months prior to leukapheresis; 4. Anti-CD20 monoclonal antibody within 7 days prior to leukapheresis; 5. Venetoclax within 4 days prior to leukapheresis; 6. Idelalisib within 2 days prior to leukapheresis; 7. Lenalidomide within 1 day prior to leukapheresis; 8. Therapeutic doses of corticosteroids (defined as prednisone or equivalent \>20 mg/day) within 7 days prior to leukapheresis; physiological replacement, topical, and inhaled steroids are permitted; 9. Non-lymphocytotoxic chemotherapy within 1 week prior to leukapheresis. Oral chemotherapy drugs are allowed if at least 3 half-lives have passed prior to leukapheresis; 10. Lymphocytotoxic chemotherapy (e.g., cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan) within 2 weeks prior to leukapheresis; 11. Investigational drugs within 4 weeks prior to leukapheresis. However, subjects who had no response or disease progression during experimental treatment and for whom at least 3 half-lives have passed since the last dose prior to leukapheresis are allowed; 12. GvHD therapy (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutic agents, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL6, or anti-IL6R) within 4 weeks prior to leukapheresis and AbTCR (anti-CD19/CD22)-T cell infusion; 13. Donor lymphocyte infusion (DLI) within 6 weeks prior to AbTCR (anti-CD19/CD22)-T cell administration; 14. Radiotherapy within 6 weeks prior to leukapheresis, including large bone marrow areas such as the sternum or pelvis. Patients with progressive disease at irradiated sites or PET-positive lesions at non-irradiated sites are eligible. Radiotherapy to a single site is allowed within 2 weeks prior to leukapheresis if there are PET-positive lesions at other non-irradiated sites; 15. If prior immunotherapy such as anti-PD1 or anti-PD-L1 was used, at least 5 half-lives must have passed between the last dose and AbTCR (anti-CD19/CD22)-T cell infusion; 12. Prior allogeneic hematopoietic stem cell transplantation; 13. Other conditions considered inappropriate by the researcher.