Polymer-lipid Particle-delivered CAR1920 mRNA CAR-T Therapy for Relapsed/Refractory B-cell Lymphoma/Leukemia

Exclusion Criteria13

• Previous receipt of any form of chimeric antigen receptor (CAR) cell therapy or other genetically modified T-cell therapies;
• History of severe immediate-type hypersensitivity reactions to commonly used drugs such as aminoglycoside antibiotics;
• Known history of Human Immunodeficiency Virus (HIV) infection, active Hepatitis B Virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics (active HBV infection is defined as meeting all three of the following criteria: a. HBV DNA quantitation ≥ 2000 IU/ml; b. ALT ≥ 2 × Upper Limits of Normal (ULN); c. Exclusion of hepatitis caused by other factors such as the disease itself or medications. If a patient was diagnosed with active HBV infection initially and converted to inactive HBV infection after anti-HBV treatment, they may be included in this study with adequate ongoing anti-HBV treatment);
• Hepatic or renal impairment unrelated to hematologic malignancies (e.g., lymphoma): ALT \> 3 × ULN, AST \> 3 × ULN, TBIL \> 2 × ULN, or serum creatinine clearance \< 30 mL/min;
• History of myocardial infarction, cardiac angioplasty, coronary artery stenting, unstable angina pectoris, active arrhythmia, or other clinically significant cardiovascular diseases within 12 months prior to enrollment;
• Other severe medical conditions that may affect the study (e.g., poorly controlled diabetes mellitus, gastric ulcer, other severe cardiorespiratory diseases, concurrent severe autoimmune diseases or congenital immunodeficiencies, uncontrolled severe infections, etc.), as well as other diseases with a high risk of condition deterioration; patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and still have acute graft-versus-host disease (GVHD) 1 month after discontinuing immunosuppressants. The decision is at the investigator's discretion;
• History of severe immediate-type hypersensitivity reactions to any specific drugs required in this study; or history of severe hypersensitivity to biological products (including antibiotics);
• Female subjects who are pregnant or lactating (due to potential risks of treatment to the fetus or infant);
• Subjects judged by the investigator to be unable to complete all scheduled visits, investigations, or diagnostic and therapeutic procedures required by the study protocol (including medium- and long-term follow-up visits), those with poor willingness to participate, those who are unwilling to join or fully cooperate with the study arrangements, or those with insufficient compliance of the subject and their family members. The decision is at the investigator's discretion;
• Concurrent progressive malignant tumors of other types; or a history of other malignant tumors, except for non-melanoma skin cancers and carcinoma in situ (e.g., of the cervix, bladder, or breast). Subjects with a history of other malignant tumors are ineligible unless they have been disease-free and not received any form of anti-tumor treatment for at least 3 consecutive years;
• History of live vaccine vaccination within 6 weeks prior to the start of the conditioning regimen;
• Receipt of major surgical procedures (excluding lymph node biopsy) within the past 14 days, or anticipated need for major surgery during the treatment period;
• Other severe physical or mental illnesses or laboratory abnormalities that may increase the risk of study participation or interfere with study results, as well as patients deemed unsuitable for participation by the investigator.