As a phase I clinical research，this study plans to evaluate the safety and tolerability of CD70-targeting CAR-T cells in the treatment of CD70-positive advanced/metastatic solid tumors, and obtain recommended doses and infusion patterns.

This is a single-center, double-arm, open-label study. The research designs to follow 2 groups：Intravenous infusion group and Intraperitoneal injection group；each group sets up 2 phases,the first phase is dose discovery phase to obtain recommended doses,the second phase is dose expansion phase to verify the safety in the recommended doses. In the discovery phase,each group puts up 4 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 12 subjects with CD70-positive advanced/metastatic solid tumors.In the dose expansion phase,each group will choose one or two dose groups to verify the safety and efficacy at this dose,and plan to recruit about 6 subjects in each dose group.

Inclusion Criteria:

1. Age ≥18 years old, male or female;

2. Advanced/metastatic solid tumor confirmed by histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimen) (positive tumor CD70 expression (tumor CD70 positive (IHC 3+) confirmed by histology or pathology)) ;

3. At least after TKI/PARPi, anti-vascular drug treatment is ineffective, there is no available standard treatment plan or standard treatment fails or intolerable (disease progression or intolerance such as surgery, chemotherapy, radiotherapy, targeted therapy, etc.), There is currently no effective treatment;

4. Measurable and evaluable lesions defined by RECIST version 1.1: Measurable disease is defined as at least one lesion that can be accurately measured on at least one level (long diameter needs to be recorded); ), when measured by magnetic resonance imaging (MRI), each lesion must be >10mm, The lymph node must be >15mm in the short axis;

5. ECOG 0-2 points (Appendix 2);

6. The expected survival time is more than 12 weeks;

7. No serious mental disorder;

8. The functions of important organs are basically normal:

   1. Hematopoietic function: neutrophils 1.0×109/L, platelets 75×109/L, hemoglobin 80g/L;
   2. Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;
   3. Renal function: serum creatinine≤2.0×ULN;
   4. Liver function: ALT and AST ≤2.0×ULN (for patients with liver tumor infiltration, it can be relaxed to ≤3.0×ULN);
   5. Total bilirubin ≤2.0×ULN (Gilbert syndrome or combined liver tumor infiltration can be relaxed to ≤3.0×ULN);
   6. Oxygen saturation > 92% in non-oxygen state.

9. Have apheresis or venous blood collection standards, and have no other contraindications for cell collection;

10. Subjects agree to use reliable and effective contraceptive methods for contraception within 1 year after signing the informed consent form to receiving CAR-T cell infusion (excluding rhythm contraception);

11. Subjects or their guardians agree to participate in this clinical trial and sign the ICF, indicating that they understand the purpose and procedures of this clinical trial and are willing to participate in the research.

Exclusion Criteria:

1. Received anti-CD70 drug treatment before screening;

2. Active/symptomatic central nervous system metastases or meningeal metastases at the time of screening; subjects with brain metastases who have been treated must be confirmed to have no imaging evidence of progression ≥ 4 weeks after the end of treatment before they can be enrolled;

3. Received any of the following treatments before screening:

   1. Participated in other interventional clinical studies before screening, including: the last use of unmarketed new drugs is less than 3 months before cell reinfusion, or the last use of marketed drugs is less than 5 half-lives from cell reinfusion;
   2. Received anti-tumor therapy such as chemotherapy and targeted therapy within 2 weeks or at least 5 half-lives (whichever is shorter) before apheresis;
   3. Received systemic corticosteroid therapy at doses greater than 10 mg/day prednisone (or equivalent doses of other corticosteroids) within 2 weeks prior to apheresis (inhalation or topical allowed in the absence of active autoimmune disease Use steroids and adrenal corticosteroid replacement at doses greater than 10 mg/day of prednisone);
   4. Received live attenuated vaccine within 4 weeks before screening;

4. Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening;

5. Malignant tumors other than the target tumor within 3 years before screening, except for the following: malignant tumors that have received radical treatment, and no known active disease within ≥ 3 years before enrollment; or Treated non-melanoma skin cancer with no evidence of disease;

6. Suffering from any of the following heart diseases:

   1. New York Heart Association (NYHA) stage III or IV congestive heart failure;
   2. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
   3. Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration);
   4. History of severe nonischemic cardiomyopathy.

7. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.;

8. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is greater than the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood type C Hepatitis virus (HCV) RNA titer detection greater than normal range Human immunodeficiency virus (HIV) antibody positive; syphilis positive test; cytomegalovirus (CMV) DNA test positive;

9. The subject has experienced venous thromboembolic events (for example: pulmonary embolism) and still needs anticoagulation therapy, or meets the following conditions: a. Bleeding with grades 3 to 4 for more than 30 days; b. There are venous Sequelae caused by embolism (such as persistent dyspnea and hypoxia); Arterial embolism but those who do not meet the above conditions can participate in the trial);

10. Poorly controlled hypertension, defined as systolic blood pressure ≥150mmHg and/or diastolic blood pressure ≥90mmHg (blood pressure values are measured based on the average of 3 readings at least 2 minutes apart, blood pressure ≥150/90mmHg at initial screening Receive antihypertensive treatment, if the treatment is well controlled and blood pressure is less than 150/90mmHg, screening can be performed);

11. Women who are pregnant or breastfeeding, and male or female subjects who plan to have children within 1 year after receiving CAR-T cell reinfusion;

12. Other investigators deem it unsuitable to participate in the study.