This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19/22 CART cells combined with PD-1 Inhibitor in relapsed/refractory B Cell Lymphoma.

Though response rates have greatly improved with the development of Chimeric antigen receptor T cells (CART) therapy in refractory/relapsed B cell non-Hodgkin's lymphoma (R/R B-NHL), the response can't usually last long and relapse occurs in a large proportion of patients who receive CART cells infusion. The main reasons of relapse might be tumor antigen loss and a lack of CART cell persistence. Currently, preclinical studies have shown that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. In parallel, the combined use of CART-19 and CART-22 cells has a better potential to reduce antigen escape and increase anti-tumor activity. Therefore, the combination of CD19/22 CART and PD-1 inhibitor is one of the ways to improve the therapeutic effect of CART cells. This study was conducted to explore the efficacy and safety of CD19/22 CART cells in R/R B-NHL.

Inclusion Criteria:

1. R/R B-NHL with measurable (≧1.5cm) lesions confirmed by pathological immunohistochemistry or flow cytometry ( meeting any of the following conditions):

   A.The lesion shrinkage <50% or disease progression after 4 courses of standard first-line treatment or 2 courses of two-line treatment (primary refractory disease) B. Progress disease as the best response after hematopoietic stem cell transplantation C.Progress disease or stable disease as the best response to most recent therapy regimen

2. Age ≥ 18 years

3. The Eastern Cooperative Oncoloy Group (ECOG) physical condition score ≤ 2 points

4. The main organ functions need to meet the following conditions:

   A.Left ventricular ejection fraction ≥50% B.Creatinine ≤132umol/l or creatinine clearance ≥60 ml/min C.ALT and AST≤2 upper limitation of normal D.SpO2 > 90%

5. Results of pregnant test should be negative, and agree to conception control during treatment and 1 year after CAR-T infusion

6. Expected survival exceeds 3 months

7. Written informed consent could be acquired

Exclusion Criteria:

1. Immunosuppressant medications or steroids was used within 2 weeks before cell collection, or need to use steroids or immunosuppressant medications more than two years
2. Uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infection
3. Active hepatitis B or hepatitis C infection
4. HIV infection
5. Severe acute or chronic graft-versus-host disease (GVHD)
6. Participated in any other drug research clinical trials within 30 days before enrollment
7. Prior CART cells therapy within 3 months before enrollment
8. Prior allogeneic hematopoietic stem cell transplantation within 6 months before enrollment
9. Have contraindications to the PD-1 inhibitors
10. Uncontrolled other tumor
11. Women in pregnancy,lactation or planning to become pregnant
12. The researcher considers inappropriate to participate in this research