Inclusion Criteria:
Subjects must meet the following criteria for inclusion in the study： 1) Male or female
subjects between the ages of 18 and 75（including critical values）； 2) Subjects
histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL), transformed
follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and mantle cell
lymphoma (MCL) ：
a） Refractory B-NHL ：Subjects of which the best response to standard first-line treatment
is PD,(those intolerant to first-line treatment will not be included in this study).
Subjects of which the best response to at least four courses of first-line treatment is SD,
with a duration of SD less than 6 months after the last treatment. Subjects of which the
best response to the last course of second-line treatment or above treatments is PD or the
best response to at least two courses of second-line treatment or above treatments is SD,
with a duration of SD less than 6 months.
b） Relapsed B-NHL：The disease relapses confirmed by histopathology in subjects who achieved
complete remission after standard systematic treatment and second-line treatment. Or the
disease relapses confirmed by histopathology within 1 year after hematopoietic stem cell
transplantation (not limited to the previous therapeutic regimen) ； c） Previous treatment
must include CD20 monoclonal antibody (except patients with CD20 negative B cell NHL) and
anthracycline； d） Subjects with TFL must receive chemotherapyInclusion criteria： Subjects
must meet the following criteria for inclusion in the study：
1. Male or female subjects between the ages of 18 and 75（including critical values）；
2. Subjects histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL),
transformed follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and
mantle cell lymphoma (MCL) ：
1. Refractory B-NHL ：Subjects of which the best response to standard first-line
treatment is PD,(those intolerant to first-line treatment will not be included in
this study). Subjects of which the best response to at least four courses of
first-line treatment is SD, with a duration of SD less than 6 months after the
last treatment. Subjects of which the best response to the last course of
second-line treatment or above treatments is PD or the best response to at least
two courses of second-line treatment or above treatments is SD, with a duration
of SD less than 6 months.
2. Relapsed B-NHL：The disease relapses confirmed by histopathology in subjects who
achieved complete remission after standard systematic treatment and second-line
treatment. Or the disease relapses confirmed by histopathology within 1 year
after hematopoietic stem cell transplantation (not limited to the previous
therapeutic regimen) ；
3. Previous treatment must include CD20 monoclonal antibody (except patients with
CD20 negative B cell NHL) and anthracycline；
4. Subjects with TFL must receive chemotherapy before transformation and meet the
above definition of relapse or refractory after transformation.
3. According to Lugano response criteria 2014, there should be at least one evaluable
tumor focus: the longest diameter of intranodal focus > 1.5cm, the longest diameter of
extranodal focus > 1.0cm；
4. Positive expression of CD19 or CD22 in tumor tissue；
5. Subjects who have no effect or relapse after single-target CAR-T treatment can also be
included in the group.
6. Approved anti-tumor therapies, such as systemic chemotherapy, systemic radiotherapy,
and immunotherapy, have been completed for at least 2 weeks before the precondition.
7. ECOG≤1；
8. Life expectancy ≥ 3 months；
9. Neutrophil absolute count ≥ 1×10^9/L；
10. platelet count ≥ 50×10^9/L；
11. Absolute lymphocyte count ≥ 1×10^8/L ；
12. Adequate organ function reserve :
1. GPT, GST ≤ 2.5× UNL（upper normal limit）；
2. Creatinine clearance (Cockcroft Gault method）≥60mL/min；
3. Serum total bilirubin ≤1.5× UNL；
4. The left ventricular ejection fraction (LVEF) ≥ 50% was diagnosed by
echocardiography, and there was no clinically significant pericardial effusion
and ECG abnormality；
5. Basic oxygen saturation in indoor natural air environment > 92%；
13. It can establish the venous access needed for collection without the contraindications
of leukocyte collection；
14. For female subjects of childbearing age, results are negative in urine pregnancy test
before screening and administration, and subjects agree to take effective
contraceptive measures at least one year after infusion; Male subjects with partners'
fertility must agree to use effective barrier contraceptive methods at least one year
after infusion, and avoid sperm donation；
15. Voluntary signing of informed consent;
Exclusion Criteria:
Any of the following points shall be deemed as no entry into this study：
1. Other tumors except cured non-melanoma skin cancer, cervical cancer in situ,
superficial bladder cancer, breast duct cancer in situ, or other malignant tumors with
complete remission of more than 5 years)；
2. Severe mental disorders；
3. A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman
syndrome, or any other known bone marrow failure syndrome；
4. History of allogeneic stem cell transplantation；
5. Heart disease with grade III-IV heart failure [NYHA classification], myocardial
infarction, angioplasty or stenting, unstable angina or other heart diseases with
prominent clinical symptoms within one year before admission；
6. Subjects with any indwelling catheter or drainage tube (such as percutaneous
nephrostomy tube, bile drainage tube or pleura/peritoneum/pericardium catheter),
should be excluded. (Special central venous catheter is allowed)；
7. Subjects with a history of CNS lymphoma, CSF malignant cells, or brain metastasis；
8. Subjects with a history of CNS disease,such as epilepsy, cerebral ischemia/hemorrhage,
dementia, cerebellar disease, or any autoimmune disease involving CNS；
9. Any of the following virological ELISA results are positive: HIV antibody, HCV
antibody, TPPA, HBsAg；
10. Active infection requiring systematic treatment within 2 weeks before single
collection；
11. Subjects with known severe allergic reactions to cyclophosphamide or fludarabine, or
diagnosed as the allergy；
12. History of autoimmune diseases (e.g. Crohn disease, rheumatoid arthritis, systemic
lupus erythematosus) that cause end-organ damage or require systemic immunosuppressive
medications or systemic disease modifying drugs in the past 2 years；
13. Presence of pulmonary fibrosis；
14. Subjects who have received other clinical trial treatment within 4 weeks before
participating in this trial should be excluded. Or the signing date of informed
consent is within 5 half-lives of the last application of another clinical trial
(whichever is longer)；
15. Subjects with poor compliance due to physiological, family, social, geographical and
other factors, or those unable to cooperate with the study plan or follow-up；
16. At the discretion of the investigator, there are complications requiring systemic
corticosteroid therapy (≥ 5mg / day of prednisone or equivalent dose of other
corticosteroids) or other immunosuppressive drugs within 6 months after this clinical
research treatment；
17. The lactating woman who is reluctant to stop breastfeeding；
18. Any other condition considered unsuitable by the investigator.
