Inclusion Criteria:

• Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification:
  • DLBCL not otherwise specified (NOS);
  • High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements;
  • High-grade B cell lymphoma, NOS o Primary mediastinal (thymic) large B cell lymphoma;
  • Transformed lymphoma (e.g., transformed follicular or marginal zone lymphoma, follicular lymphoma Grade 3).
• Relapsed or refractory disease after 2 or more lines of chemotherapy including rituximab and anthracycline and either having failed autologous stem cell transplant (ASCT), or being ineligible for or not consenting to ASCT 2.1.
• Chemotherapy-refractory disease is defined as one of the following:
  • No response to last line of therapy:
  • Progressive disease (PD) as best response to most recent therapy regimen o Stable disease (SD) as best response to most recent therapy with duration no longer than 6 months from last dose of therapy; OR
  • Relapsed or persistent disease after prior ASCT for lymphoma;
    • Disease progression or relapse less than or equal to 12 months of ASCT;
    • If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.
• Disease relapse in subjects without prior ASCT is defined as relapse of disease in ≤ 12 month after the last dose of most recent therapy regimen.
• Ineligible for ASCT is defined as meeting one of the following criteria:
  • Chemotherapy-refractory disease after salvage therapy;
  • Disease progression or relapse ≤ 12 months after salvage therapy;
  • Intolerance to salvage therapy.
• In addition, all subjects must have:
  • Age ≥ 18 years;
  • Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to DLBCL;
  • Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma (Cheson et al, 2014);
  • CD19 or CD20 antigen expression on tumor is not required after the most recent chemoimmunotherapy; however:
    • Subject must have at least 10 unstained slides of tissue available prior to MB-CART2019.1 infusion;
    • If archival tissue is not available, subject must be willing to undergo attempted repeat biopsy.
  • No clinical suspicion of central nervous system (CNS) lymphoma.
• If the subject has history of CNS disease, then he/she must:
  • Have no signs or symptoms of CNS disease;
  • Have no active disease on magnetic resonance imaging (MRI);
  • Have no large cell lymphoma present in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells (WBCs).
• If has history of cerebral vascular accident (CVA):
  • The CVA event must be greater than 12 months prior to leukapheresis;
  • Any neurological deficits must be stable.
• A creatinine clearance (as estimated by direct urine collection) > 60mL/min.
• Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA).
• Resting O2 saturation > 90% on room air.
• Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) 1000/μL.
• Absolute lymphocyte count > 100/μL.
• Platelet count > 50,000/µL.
• Estimated life expectancy of more than 3 months other than primary disease.
• Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study.

Exclusion Criteria:

• Primary CNS lymphoma.
• Richter’s transformed DLBCL arising from chronic lymphocytic leukemia (CLL).
• Unable to give informed consent.
• Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive), unless confirmed to be polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive.
• Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing
• Known history of active seizure or presence of seizure activities or on active anti-seizure medications within the prior 12 months.
• Known history of CVA within prior 12 months.
• Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease.
• Presence of active CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity.
• Active systemic fungal, viral or bacterial infection.
• Pregnant or breast-feeding woman.
• Previous or concurrent malignancy with the following exceptions:
  • Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry);
  • In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study;
  • Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years;
  • A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years.
• History of non-neurologic autoimmune disease (e.g., Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus) requiring systemic immunosuppressive or systemic disease modifying agents within the last 2 years.
• Medical condition requiring prolonged use of systemic corticosteroids equivalent to Prednisone > 10 mg/day.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment.
• Concurrent radiotherapy (allow up to time of leukapheresis).
• Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Refusal to participate in additional lentiviral gene therapy long-term follow-up (LTFU) protocol.
• Prior CAR-T therapy for any indication.
• Prior allogeneic stem cell transplant for any indication.
• Prior Bispecific T cell engaging (BITE) antibodies for cancer therapy.
• Prior T cell receptor-engineered T cell therapy.