Anti-CD70-CAR-T Cell Injection for the Treatment of Locally Advanced or Relapsed/Metastatic CD70+ Inoperable Renal Cells

Inclusion Criteria:

1. Understand and sign informed consent, and voluntarily participate in clinicalresearch;

2. Age ≥18, and <70 years old, gender is not limited;

3. Histopathologically or cytologically confirmed advanced malignant renal cellcarcinoma of CD70+ with at least VEGFR-targeted therapy and an immune checkpointtherapy (either combination therapy or sequential therapy);

4. At least one measurable lesion with a maximum diameter of less than 6 cm accordingto RECIST 1.1;

5. Expected survival ≥12 weeks;

6. ECOG score ≤2 points;

7. Have sufficient hematologic function and have not received blood transfusion or cellgrowth factor therapy within 7 days prior to the hematologic evaluation during thescreening period (2 weeks interval is required for those receiving long-actingagents such as PEG-rhG-CSF, allowing the use of recombinant erythropoietin) :

• Neutrophil absolute value ≥1.5×109/L

• Hemoglobin ≥80g/L

• Platelets ≥75×109/L

• Lymphocytes (ALC) ≥0.3×109/L

8. Adequate liver function: serum total bilirubin ≤1.5× upper limit of normal (ULN) (for Gilbert syndrome patients, total bilirubin ≤3×ULN), aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5×ULN; If there is liver metastasis, allowAST, ALT≤5×ULN);

9. Adequate renal function: creatinine ≤1.5×ULN or endogenous creatinine clearance ≥50mL/min (using Cockcroft Gault formula);

10. Left ventricular ejection fraction (LVEF) of echocardiography was ≥50%.

11. There was no evidence of dyspnea at rest and pulse oximetry was >93% without oxygen.

12. Activated partial thromboplastin time (APTT) ≤1.5×ULN and International normalizedratio (INR) ≤1.5×ULN;

13. Good venous access (for apheresis) and no other contraindications for blood cellseparation;

14. Pregnancy tests for women of childbearing age must be negative. All subjects mustagree to use an effective contraceptive method at the same time from the time ofsigning the informed consent to 12 months after the final administration of thestudy drug.

Exclusion Criteria:

Patients are not eligible to participate in this trial if they meet any of the following conditions:

1. Previous use of any CAR T cell products or other genetically modified T celltherapy;

2. Patients who have a history of allogeneic stem cells or solid organ transplantationor are waiting for organ transplantation;

3. Patients with acute or uncontrolled active infection who currently requireintravenous anti-infective therapy, and patients taking antibiotics to preventinfection should be allowed to participate in the study at the discretion of theinvestigator;

4. Active hepatitis B (hepatitis B surface antigen positive and hepatitis B DNA>103copies /mL or >200IU/mL), active hepatitis C (hepatitis C antibody positive and RNApositive); Active syphilis infection (RPR or TRUst-positive), human immunodeficiencyvirus (HIV) infection (HIV positive);

5. Patients with low sodium and/or hypokalemia with blood sodium <125mmol/L and/orblood potassium <3.5mmol/L (unless sodium and/or potassium supplementation isrequired prior to study participation to restore blood sodium and/or potassium abovethis level);

6. Imaging results showed that the proportion of liver replaced by tumor was ≥50%;

7. There was clinically uncontrollable third space effusion, which was judged by theresearcher not suitable for inclusion;

8. Previously received anti-CD70 therapy;

9. Receiving continuous systemic steroid medication (prednisone > 10mg/ day orequivalent dose of other hormones) within 14 days of preapheresis or 3 days beforecell therapy, except for recent or current topical steroid use;

10. Toxicity from previous antitumor therapy has not recovered (>CTCAE version 5.0 Grade 1), except for alopecia, pigmentation, and other tolerable events as determined bythe investigator or laboratory abnormalities permitted under the protocol;

11. The eluting period of preaphermative antitumor therapy met the followingrequirements:

• ≦2 weeks or 5 half-lives of chemotherapy, small molecule targeted therapy,radiotherapy, endocrine therapy, immunomodulatory therapy, and Chinese medicinewith anti-tumor indications

• ≦4 weeks of macromolecular targeted therapy and immunotherapy

• ≦4 weeks of anti-tumor vaccine

• ≦4 weeks of investigational medication/therapy

12. Previous or current co-occurrence of other malignancies (other than basal cellcarcinoma of the skin, carcinoma in situ of the breast/cervix and other malignanciesthat have been cured or are free of disease and have not been treated in the pastfive years);

13. Previous history of primary or secondary tumors of the central nervous system (CNS) (except stable ≥4 weeks after treatment, no current CNS related signs and no drugcontrol ≥14 days);

14. Patients with other central nervous system diseases (such as seizures, cerebralhemorrhage, dementia, etc.) that researchers have judged may affect the safety ofsubjects;

15. Uncontrolled hypertension (systolic blood pressure ≥150 MMHG and/or diastolic bloodpressure ≥95mmHg after standard treatment), unstable angina, congestive heartfailure of New York Heart Association grade III or higher, or significantabnormalities on ECG, Severe arrhythmias requiring treatment and a history ofmyocardial infarction within 6 months prior to initiation of study therapy;

16. Patients with severe respiratory diseases, such as interstitial lung disease, activepulmonary tuberculosis, and patients who have received extensive radiation therapyin the lung, were not considered suitable for inclusion by researchers;

17. Patients with active or past autoimmune diseases with the possibility of recurrence (e.g. systemic lupus erythematosus, rheumatoid arthritis, etc.), except for type 1diabetes, hypothyroidism requiring hormone replacement therapy, skin diseaseswithout systemic treatment (e.g. vitiligo, psoriasis or alopecia);

18. In the investigator's judgment, any serious or uncontrollable systemic disease,systemic comorbiditis, other serious comorbiditis (such as hemophagic cell syndrome,etc.), or special conditions of the tumor may make the patient unfit to enter thestudy or affect protocol compliance, or significantly interfere with the correctevaluation of the safety, toxicity, and effectiveness of the investigatory drugs;

19. Had any major surgery (other than exploratory laparotomy or laparoscopicexploration) or severe trauma within 4 weeks prior to apheresis, had major surgeryscheduled during DLT observation, or had not fully recovered from any previousinvasive procedure;

20. Patients who are allergic to or intolerant to antisepsis agents that may be usedduring the study or to medications that are appropriate for the treatment of CRS,including but not limited to fludarabine and cyclophosphamide or toluzumab; Known tobe allergic to anti-CD70-CAR-T ingredients; Or have any history of severe allergies,such as anaphylactic shock;

21. Women who are pregnant, who plan to become pregnant during the trial, or who arebreastfeeding;

22. Patients judged by the investigator to be unable or unwilling to comply withclinical protocols;

23. Persons involved in the planning and execution of the research.