In this single-center, single-arm,prospective, open-label, phase 1/2 study, the safety and efficacy of autologous CD70 targeted chimeric antigen receptor modified T (CAR-T) cell therapy will be evaluated in patients with CD70 antigen positive Relapsed/Refractory Lymphoma . In this clinical trial, at least 12 eligible patients in dose escalation period will be enrolled to receive 3 doses of CD70-CAR cell therapy according to the "3+3" principle. In dose expansion period, additional at most 21 eligible patients will be enrolled to receive CD70-CAR-T cell therapy at dose of recommended phase 2 dose(RP2D).

CAR-T cell therapy has been identified as a breakthrough therapy in hematologic malignancies,especially anti-CD19 CAR-T cell therapy in the treatment of r/r B-NHL has achieved remarkable efficacy.However, relapse with CD19-negative tumor after treatment with anti-CD19 CAR-T cells has been reported in different types of B-cell lymphoid malignancies, with a percentage up to 38% in patients with non-Hodgkin lymphoma (NHL).At present, the CAR-T cell treatment for HL is mainly confined to CD30 antigen,with an objective response rate (ORR) only 38%~62%. Therefore, a more effective treatment strategy is needed for these patients.

CD70, the membrane-binding ligand of the CD27 (a tumor necrosis factor receptor superfamily), has been reported to mediate tumour cell proliferation and be expressed on the malignant cells of diffuse large B-cell lymphoma (DLBCL)，mantle cell lymphoma (MCL) and follicular lymphomas (FL), as well as Hodgkin lymphoma, etc,but rarely on normal B cells or T cells,indicating CD70 targeted treament has emerged as potentialnovel immunotherapeutic strategy.Preclinical study demonstrated CD70-CAR-T cells represent a new therapeutic option for the treatment of patients with CD19-negative recurrence of lymphoma.Based on the preclinical data, we conduct this clinical trial in order to test the the safety profiles and anti-tumor activities of CD70-CAR-T cells in vivo. In dose escalation period, at least 12 eligible patients will be enrolled and receive 3 doses of CD70-CAR-T cell therapy (1 × 10^6 cells/kg, 3 × 10^6 cells/kg, 1 × 10^7 cells/kg) according to the "3+3" principle. In dose expansion period, additional at most 21 eligible patients will be enrolled to receive CD70-CAR-T cell infusion at dose of RP2D, which is determined by data from dose escalation period, including occurrence of dose limiting toxicities(DLT), pharmacokinetics/pharmacodynamics, efficacy and other parameters, to furtherly evaluate the safety and efficacy profiles of CD70-CAR-T cell therapy.

Inclusion Criteria:

Patients eligible for inclusion in this study had to meet all of the following criteria:

1. Age 18-75 (inclusive);

2. ECOG performance status ≤2 and Estimated life expectancy of more than 3 months;

3. Patients with histologically confirmed lymphoma including the following types defined by the World Health Organization(WHO) 2016:HL,Aggressive B-cell non-Hodgkin's lymphoma(Diffuse large B-cell lymphoma,High grade B-cell lymphoma,burkitt's lymphoma,Mantle cell lymph,Anaplastic large cell lymphoma, etc.) and Indolent lymphoma（Including but not limited to follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, etc.）

4. Relapse after treatment with ≥2 lines systemic therapy for all the above disease types. Relapse disease is defined as disease progression after last regimen. Refractory disease is defined as no CR tofirst-line therapy:

   • PD as best response to first-line therapy, or
   • SD as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R- CHOP), or
   • PR as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 6 months of therapy, or
   • Refractory post-autologous stem cell transplant (ASCT) i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy prove recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.
   • Individuals must have received adequate prior therapy.

5. CD70 antigen expression percentage ≥ 10%.

6. Successful leukapheresis assessment and preculture of T cells;

7. According to Lugano response criteria 2014, there should be at least one evaluable tumor focus. Evaluable tumor focus was defined as that with the longest diameter of intranodal focus > 1.5cm, the longest diameter of extranodal focus > 1.0cm assessed by computed tomography (CT) ormagnetic resonance imaging (MRI).

8. Functions of important organs meet the following requirements:ANC≥≥1×10^9/L; Platelet count ≥50×10^9/L; Hemoglobin ≥80 g/L;Serum AST and serum ALT, ≤3.0 x ULN (≤5 x ULN for patients with liver metastases); Total serum bilirubin ≤3.0 x ULN); Serum creatinine ≤1.5xULN ; Echocardiography showed left ventricular ejection fraction ≥50%.Pulmonary function: oxygen saturation of blood (SaO2) ≥92% in indoor air environment.

9. Toxicity from previous antitumor therapy ≤ grade 1 (according to CTCAE version 5.0) or to an acceptable level of inclusion/exclusion criteria (other toxicities such as alopecia and vitiligo considered by the investigator to pose no safety risk to the subject).

10. Pregnancy tests for women of childbearing age shall be negative;Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year.

11. Ability to understand and sign a written informed consent documen.

Exclusion Criteria:

1. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
2. Received cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives before enrollment;
3. Pregnant, lactating, or breastfeeding females;
4. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
5. Known positive test result for human immunodeficiency virus (HIV) oracquired immune deficiency syndrome (AIDS);Active infection of hepatitis B virus (HBV), or hepatitis C virus (HCV);
6. History of allergy or intolerance to study drug components;
7. Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation;
8. Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered.
9. Known brain metastases or active central nervous system(CNS) has been involved
10. Previous or concurrent cancer within 5 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer, local prostate cancer after radical surgery ;
11. Any serious underlying medical (eg, pulmonary, renal,hepatic,gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements;
12. Vaccination within 30 days of study enrollment;
13. Previously received targeting CD70 therapy;
14. Being participating any other trials or withdraw within 4 weeks;
15. Researchers believe that other reasons are not suitable for clinicaltrials.