Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical Research

Inclusion Criteria: * The patient or his/her guardian voluntarily signed the informed consent * Adult Patients clinical diagnosis of relapsed and refractory diffuse large B-cell lymphoma (Primary mediastinal large B-cell lymphoma and transformed follicular lymphoma are included) Definition of refractory: 1. No response to the last treatment, including: The best response to the last treatment was PD, or ; The best response to the last treatment was SD and the duration was not more than 6 months after the last dose. 2. Not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including: Disease progression or recurrence within 12 months or less (recurrence must be confirmed by biopsy) after ASCT treatment, or; Patients accept remedial treatment after ASCT must have no response or relapse after the last treatment * Patients who had previously received ≥2 lines therapy including at least: 1. A chemotherapy regimen containing anthracyclines 2. For patients with transformed DLBCL from follicular lymphoma, they must have previously received chemotherapy for follicular lymphoma and have refractory disease after transformation to DLBCL. * Patients with double-strike and triple-strike lymphoma who do not respond to second-line treatment, where double-strike/triple-strike is defined as: Detection of lymphoma cells with C-MYC gene translocation accompanied by BCL-2 gene translocation or/and BCL-6 gene translocation by chromosome or FISH technology. * CD19 expression was positive by immunohistochemistry or flow cytometry (accept the results of this peripheral blood mononuclear cells or previous report from a Class A tertiary hospital before peripheral blood collection) * At least one measurable lesion at baseline, according to the initial assessment, staging and Response Assessment recommendations for Hodgkin's and non-Hodgkin's lymphoma (2014 edition) * Expected survival time greater than 12 weeks * The baseline ECOG score was 0 or 1 * Organ function: 1. Kidney function is defined as: Serum creatinine ≤1.5 times ULN, or; The glomerular filtration rate (eGFR) estimated by MDRD formula was ≥60m/ min/1.73m2; \[eGFR=186×(age)-0.203×SCr- 1. 154(mg/dl), for females, the result was ×0.742\] 2. Liver function is defined as: ALT≤5 times ULN, and; Patients with total bilirubin ≤2.0mg/dl, except those with Gilbert-Meulengracht syndrome. Patients with Gilbert-Meulengracht syndrome with total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN were included 3. Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) ≥91% in indoor air environment. * Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45% * Patients using the following drugs must meet the following conditions: 1. Steroid: Therapeutic doses of steroids must be discontinued 2 weeks prior to Meta10-19 infusion. However, physiological replacement doses of steroids are permitted, hydrocortisone or its equivalent \<6-12mg/mm2/ day 2. Immunosuppressive agent: Any immunosuppressive drug must be stopped ≥4 weeks before the informed consent is signed 3. Anti-proliferative therapy in addition to preconditioning chemotherapy 2 weeks prior to Meta10-19 infusion 4. Treatment for CNS disease must be stopped 1 week before Meta10- 19 infusion (e.g., intrathecal methotrexate) * The patient has recovered from the toxicity of the previous treatment, that is, the CTCAE toxicity grade is less than 1 (The exception is specific toxicity of grade 2 or less, such as hair loss, which the researchers have determined is not recoverable in a short period of time) is suitable for pretreatment chemotherapy and CAR T cell therapy * Women of childbearing age and all male patients must consent to use a effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR T cells in vivo Exclusion Criteria: * Patients with present or history of central nervous system diseases such as seizures disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement * Patients with history of allogeneic hematopoietic stem cell transplantation * Patients who had received chemotherapy other than preconditioning chemotherapy within 2 weeks prior to Meta10-19 infusion * Patients who participated in other clinical trials within 30 days prior to enrollment * Patients with active hepatitis B (defined as hepatitis B surface antigen positive or hepatitis B core antibody positive, concomitant hepatitis B virus DNA level \>1000 copies/ml) or hepatitis C (HCV RNA positive) * Patients with HIV antibody positive or treponema pallidum antibody positive * Patients with uncontrolled acute life-threatening bacterial, viral or fungal infections (e.g. positive blood cultures ≤72 hours before Meta10-19infusion) * Patients with unstable angina pectoris and/or myocardial infarction within 6 months prior to enrollment * Patients with history of other malignancies, but the following conditions can be enrollment: 1. Adequately treated basal or squamous cell carcinoma (requiring adequate wound healing before signing informed consent); 2. Carcinoma in situ (DCIS) of cervical or breast cancer, which has been treated therapeutically, has shown no signs of recurrence for at least 3 years prior to the signing of the informed consent 3. The primary malignancy has been completely resected and in complete remission for ≥5 years * Women who are pregnant or breastfeeding (pregnancy tests for women of childbearing age are positive) * Patients with active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre syndrome, amyotrophic lateral sclerosis); * Other conditions that the investigator considered should not be enrolled in this clinical study, such as poor compliance.