Inclusion Criteria:
* Patients with refractory/recurrent CNS lymphoma must meet all of the following criteria to be eligible:
1. Voluntarily participate in the study and sign the informed consent;
2. Age 18-75 years old, male or female;
3. Diffuse large B-cell lymphoma (DLBCL) was confirmed by histology. CD19 expression was positive by lymphoma pathology or flow cytometry, and CD19 expression was ≥20% by IHC.
4. Imaging showed no evidence of systemic lymphoma;
5. Meets any of the following definitions for refractory/relapsed CNS lymphoma: no complete response has been achieved with prior 2-line regimen including methotrexate or cytarabine-based regimen; Disease progression during any treatment; The stable time of disease after effective treatment is less than 6 months; Disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation.
6. Imaging showed the presence of at least one measurable lesion, with a minimum diameter of ≥10mm;
7. Expected survival ≥3 months;
8. ECOG score 0-3 points;
9. Adequate organ function reserve:
* alanine aminotransferase, ASpartate aminotransferase ≤ 2.5× UNL (upper limit of normal);
* Creatinine clearance (Cockcroft-Gault method) ≥60 mL/min;
* Serum total bilirubin and alkaline phosphatase ≤1.5× UNL;
* Glomerular filtration rate \>50ml/min
* cardiac ejection fraction (EF) ≥45%;
* Basic oxygen saturation \>92% in indoor natural air environment;
* Blood routine: absolute number of neutrophils \>×109/L, platelet count 45×109/L, hemoglobin 80g/L;
10. Previous autologous hematopoietic stem cell transplantation is allowed, and the interval between stem cell transfusion and CAR-NK transfusion is ≥3 months;
11. Previous CAR-T cell therapy is allowed, and the time interval between CAR-T transfusion and CAR-NK transfusion is ≥3 months;
12. Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraception during the test;
13. Approved anti-tumor therapies, such as systemic chemotherapy, whole body radiotherapy and immunotherapy, have been discontinued for at least 3 weeks before the study; Discontinuation of targeted drug regiments without chemotherapy for at least 2 weeks;
Exclusion Criteria:
* Subjects who meet any of the following criteria will not be admitted to the study:
1. Allergic to any of the components of cell products;
2. History of other tumors;
3. Acute grade II-IV (Glucksberg standard) GvHD or generalized chronic GvHD occurred after previous allogeneic hematopoietic stem cell transplantation; Or are receiving anti-GVHD treatment;
4. Have received gene therapy within the past 3 months;
5. Active infections requiring treatment (except simple urinary tract infections, bacterial pharyngitis), but prophylactic antibiotic, antiviral and antifungal infection treatment is permitted;
6. Persons infected with hepatitis B (HBsAg positive, but HBV-DNA\<103 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV-infected persons;
7. Subjects with Grade III or IV cardiac dysfunction according to the New York Heart Association's cardiac function grading criteria;
8. Patients who received antitumor therapy in the early stage but did not recover toxicity (CTCAE 5.0 toxicity did not recover to ≤ grade 1, except fatigue, anorexia, alopecia);
9. Previous history of epilepsy, autoimmune encephalitis, cerebral infarction or cerebral hemorrhage within 6 months;
10. Whole-body enhanced CT or PET/CT suggests evidence of systemic lymphoma;
11. Lactating women who are unwilling to stop breastfeeding;
12. Any other circumstances that the investigator believes may increase the risk to the subject or interfere with the test results;
13. Patients requiring more than 10mg of dexamethasone per day for 3 days prior to enrollment;
14. Patients who cannot tolerate ommaya capsule implantation;
15. Those who cannot tolerate enhanced magnetic resonance imaging.
