Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory B-cell Malignancies

Inclusion Criteria: 1. Age ≥ 18 years old, regardless of gender; 2. Eastern Cooperative Oncology Group score 0-2; 3. Participants with CD19 positive B-cell malignancies, including acute lymphocytic leukemia (all), chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL); 4. Failure or recurrence of at least 2-line treatment (including immunotherapy, targeted therapy and stem cell transplantation); 5. Measurable lesions with an expected survival of more than 3 months; 6. The functions of liver, kidney, heart and lung meet the following requirements: * creatinine clearance rate ≥ 60ml / min ; * ALT (alanine transaminase, ALT) / AST (aspartate aminotransferase, AST) ≤ 2.5 times the upper normal limit; * total bilirubin ≤ 1.5 times the upper limit of normal value, except for participants with Gilbert syndrome, the total bilirubin must be \< / = 3.0 mg / dl; * left ventricular ejection fraction ≥ 50%, no clinically significant ECG results; * blood oxygen saturation \> 92% in non oxygen absorption state; 7. The subjects agreed to use reliable contraceptive methods for contraception within 1 year from the signing of informed consent to reinfusion. Including but not limited to: abstinence, male vasectomy, implantable progesterone contraceptives that can inhibit ovulation; Intrauterine device; Hormone releasing intrauterine device; Sexual partner sterilization; Copper IUD, correct use of proven compound hormone contraceptives that can inhibit ovulation; Progesterone contraceptives that inhibit ovulation. At the same time, the subjects should promise not to donate eggs (oocytes, oocytes) / sperm for assisted reproduction within 1 year after reinfusion; 8. Voluntarily participate in clinical trials and sign informed consent. Exclusion Criteria: 1. Known allergic reaction, hypersensitivity, intolerance or contraindication to CAR NK-CD19 or any component of drugs that may be used in the study (including fludarabine, cyclophosphamide and tozumab), or subjects who have had severe allergic reaction in the past; 2. Participants with gastrointestinal lymph nodes and / or central nervous system involvement who were judged by the researchers to be at risk by CAR NK-CD19 treatment (except those who were judged by the researchers to be more likely to benefit than risk); 3. Those who have graft-versus-host response and need to use immunosuppressants; or suffering from autoimmune diseases; 4. Before screening, the researchers judged that corticosteroids needed to receive a long-term therapeutic dose during the study period; 5. Received the following anti-tumor treatment within the specified time before screening: i. Have received small molecule targeted therapy within 4 weeks or 5 half lives (whichever is longer); ii. Have received macromolecular drug treatment within 4 weeks or 2 half lives (whichever is longer); iii. Have received cytotoxic treatment or modern traditional Chinese medicine preparation with antitumor effect within 2 weeks; 6. Those who have been vaccinated with live vaccine or attenuated vaccine within 4 weeks before screening; Note: it is allowed to receive inactivated virus vaccine for seasonal influenza; However, it is not allowed to receive live attenuated influenza vaccine for intranasal use; 7. History of epilepsy or other central nervous system diseases; 8. Other active malignant tumors in the two years before screening (except for the following cases: tumors targeted in this study, surgically removed non-melanoma skin cancer, cured cervical carcinoma in situ, local prostate cancer, low-stage bladder cancer, breast ductal carcinoma in situ, or no recurrence and no treatment of malignant tumors in the two years before randomization); 9. Within 14 days before enrollment, there were active or uncontrollable infections requiring systemic treatment; 10. Active hepatitis B participants; Hepatitis C virus (HCV) antibody positive; Human immunodeficiency virus (HIV) antibody positive; Syphilis antibody positive in primary screening; a) Participants with inactive / asymptomatic carrier, chronic or active HBV infection can be included if they meet the following conditions: HBV DNA \< 500 IU / ml (or 2500 copies / ml) at the time of screening. 11. The toxicity (including peripheral neuropathy) caused by previous treatment has not fully recovered or stabilized to grade 1 (nci-ctcae V5.0) (except those that the researcher judges will not affect the patient's safe treatment, such as hair loss); 12. Heart disease: there is heart failure (NYHA classification ≥ class II, Appendix 2) and serious heart disease determined by the researcher; Myocardial infarction occurred ≤ 6 months before screening; Unstable angina pectoris, severe arrhythmia judged by the researcher or coronary artery bypass grafting (CABG) occurred ≤ 3 months before screening; 13. Poor control of hypertension (systolic blood pressure \> 160 mmHg and / or diastolic blood pressure \> 100 mmHg) or accompanied by hypertensive crisis or hypertensive encephalopathy; 14. Participants who had undergone major surgery or plasma separation other than diagnosis or biopsy within 4 weeks before screening, or were expected to undergo major surgery during the study; Note: participants who plan to perform surgery under local anesthesia can participate in the study. Kyphoplasty or laminoplasty is not considered a major operation; 15. Those who are receiving thrombolytic, anticoagulant or antiplatelet therapy; 16. The subjects judged by the researcher are difficult to complete all visits or operations required by the study protocol, or the compliance of participating in the study is insufficient.