CD70 Targeted CAR-T Cells in CD70 Positive Relapsed/Refractory Lymphoma

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.