CD70-targeted CAR-NK cell therapy for T‑cell lymphoma and acute myeloid leukemia

Inclusion Criteria:

According to the WHO disease classification, patients with relapsed/refractory T - lymphoma and acute myeloid leukemia:

1. Voluntarily participate in this study and sign the informed consent form;
2. Aged between 18-75 years old, both male and female are eligible;
3. Relapsed/refractory T cell lymphoma is defined as: relapsed/refractory after having received at least two or more lines of previous treatment (patients with anaplastic large -cell lymphoma must have been exposed and resistant to Brentuximab vedotin). The celluar subtypes of T-cell lymphoma include: angioimmunoblastic T-cell lymphoma; peripheral T - cell lymphoma not otherwise specified; ALK-negative anaplastic large - cell lymphoma; Relapsed/refractory AML is defined as: leukemia cells reappear in the peripheral blood after complete remission or the blasts in the bone marrow ≥ 5% or the extramedullary leukemia infiltration outside. Or newly diagnosed cases did not achieve a CR after two courses of standard regimens; those who relapse within 12 months after CR after consolidation and intensification treatment; those who relapse after 12 months and have not responded to conventional chemotherapy; those who relapse two or more times; those with persistent extramedullary leukemia;
4. The expected survival period ≥ 12 weeks;
5. CD70 expression is positive in tumor tissue puncture sections/tumor cells detected by flow cytometry, and the number of CD70 - positive cells detected by immunohistochemistry ≥ 20% (++ or more);
6. ECOG score is 0 - 2;
7. Adequate organ function reserve:

   * Alanine aminotransferase and aspartate aminotransferase ≤ 2.5× UNL;
   * Creatinine clearance rate (Cockcroft - Gault method) ≥ 60 mL/min;
   * Serum total bilirubin and alkaline phosphatase ≤ 1.5× UNL;
   * Glomerular filtration rate \> 50 ml/min;
   * Cardiac ejection fraction ≥ 45%;
   * Under indoor natural air environment, the basic oxygen saturation \> 92%;
   * Routine blood test: absolute neutrophil count \> 1000/mm3, platelet count ≥ 45×109, hemoglobin ≥ 8.0g/dl (the standard for AML patients is ≥ 7.0g/dl; blood transfusion is allowed);
8. Previous autologous hematopoietic stem cell transplantation is allowed once;
9. Patients who have previously received CAR - T cell therapy and were evaluated as ineffective after 3 months or relapsed after CR are allowed;
10. Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial period;
11. No active lung infection, and indoor air blood oxygen saturation ≥ 92%;
12. Before the study drug is used, approved anti - tumor treatment methods, such as systemic chemotherapy, whole - body radiotherapy, and immunotherapy, have been completed for at least 3 weeks; the wash - out period for targeted drug regimens without chemotherapy is 2 weeks;
13. Two negative tests for COVID - 19 or influenza A.

Exclusion Criteria:

Subjects meeting any of the following criteria will not be eligible for this study:

1. Those with a history of allergy to any component in the cellular product;
2. Those with a history of other tumors;
3. Those who had grade II - IV (Glucksberg criteria) acute GvHD or extensive chronic GvHD after previous allogeneic hematopoietic stem cell transplantation; or those who are currently receiving anti - GvHD treatment;
4. Those who have received gene therapy within the past 3 months;
5. Those with active infections requiring treatment (except for simple urinary tract infections and bacterial pharyngitis). However, prophylactic antibiotic, antiviral, and antifungal treatments are permitted;
6. Subjects with hepatitis B (HBsAg - positive, but HBV - DNA \< 103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis, and other acquired or congenital immunodeficiency diseases, including but not limited to those infected with the AIDS virus;
7. Subjects with grade III or IV cardiac insufficiency according to the New York Heart Association cardiac function classification standard of the United States;
8. Those whose toxic reactions from previous anti - tumor treatment have not recovered (CTCAE 5.0 toxic reactions have not recovered to ≤ grade 1, except for fatigue, anorexia, and alopecia);
9. Subjects with a history of epilepsy or other central nervous system diseases;
10. Lactating women who are unwilling to stop breastfeeding;
11. Any other circumstances that, in the opinion of the investigator, may increase the risk to the subject or interfere with the test results;
12. Those with positive nucleic acid tests for COVID - 19 or influenza A.