Safety and Efficacy of Fourth-Generation CAR-T in the Treatment of Hematologic Malignancies

Inclusion Criteria: Subjects must meet all of the following criteria to be enrolled: 1\. Voluntarily participate in this clinical study and sign the informed consent form; 2. 18 to 75 years old (including cut-off value), Male and female;; 3. Expected survival of at least 3 months; 4.1 CD19-positive B lymphocyte-derived hematologic malignancies; 4.2 Multiple myeloma patients; 4.3 Non-B cell-derived hematologic malignancies patients with CD7 or other target molecules; 5. The clinical trial values during the screening period meet the following criteria: 1. White blood cell count ≥ 3.0 × 10e9/L; Absolute neutrophil ≥ 1.0 × 10e9/L; Lymphocyte count ≥ 0.5 × 10e9/L. (The growth factor support is allowed, but growth factor must not have been received within 7 days prior to laboratory testing); 2. Platelet count ≥ 50 × 10e9/L (No blood transfusion support within 7 days prior to laboratory tests.); Note: Patients with leukemia, multiple myeloma, and lymphoma are not subject to the above blood picture requirements; 3. Biochemical indicators Serum total bilirubin (TBIL) ≤ 2.5 ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ULN, or 5 ULN if liver dysfunction is primarily due to tumor invasion); 6. Cardiac function: Subjects must have good hemodynamic stability, left ventricular ejection fraction (LVEF) ≥ 55%; 7. Lung condition: Subjects are not serious infections such as severe pneumonia; 8. ECOG activity status score: 0-2 points; 9. Female subjects must use effective contraception (such as oral prescription contraceptives, injectable contraceptives, intrauterine devices, double blockade, contraceptive patches, male partner sterilization) throughout the study period; Must have a negative serum or urine pregnancy test result at screening and throughout the study. Exclusion Criteria: Any one of the following conditions cannot be selected as a subject: 1. Having received CAR-T therapy targeting the same molecule; 2. Having received other immunotargeted therapy targeting the same molecules; 3. Pregnant or lactating women; 4. Subjects who have previously suffered from other malignancies, with the following exceptions: 1. Having received curative therapy, and no known active disease in the ≥ 3 years prior to the enrollment; 2. Non melanoma skin cancer subjects who have completed sufficient treatment and no evidence of thecurrent disease; 5. Subjects with a severe mental disorder; 6. Subjects with active autoimmune disease requiring immunotherapy; 7. Having received allogeneic hematopoietic stem cell transplantation; 8. Subjects with significant cardiovascular diseasesa.uncontrolled or symptomatic arrhythmias, congestive heart failure, or any heart disease with cardiac function grade 3 or grade 4 (according to the functional classification method of the New York Heart Association NYHA); b. Myocardial infarction or coronary artery bypass grafting within 6 months prior to screening); c. Clinically significant history of ventricular arrhythmia or unexplained syncope (non vaso-vagal or not due to dehydration); 9. Subjects with active infectious disease including positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood Hepatitis B virus(HBV) DNA titer is ≥500IU/mL, hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive, human immunodeficiency virus(HIV) antibody positive, syphilis primary screening antibody positive, active pulmonary tuberculosis; or with any significant infection requiring high-grade antibiotics Event; 10. Subjects with dysfunction of important organssuch as organ function in the following abnormalities: 1. Serum AST or ALT \> 2.5×ULN, or \> 5ULN if liver function is predominantly due to tumor invasion; TBIL \> 2.5 × ULN, unless the subject is Gilbert's syndrome; 2. Serum creatinine\>2.5mg/dl; 3. Partial prothrombin time or activated partial thromboplastin time or international normalized ratio \> 1.5×ULN in the absence of anticoagulant therapy; 11. Participation in other clinical studies or prior treatment with any gene therapy product in the past three months; 12. Subjects with uncontrolled diabetes mellitus (glycosylated hemoglobin HbAlc \>8% at screening);13. Highly allergic constitution or history of severe allergies, and having contraindications to cyclophosphamide or fludarabine; 14\. Feasibility assessment screening demonstrated \<10% transfection of targeted lymphocytes or underamplification under CD3 / CD28 costimulation (\<5-fold); 15. Subjects who are considered unsuitable to participate in this trial by the investigator.