Clinical Study of CD276 Targeted Autologous Chimeric Antigen Receptor T Cell Infusion in Patients With CD276 Positive Advanced Solid Tumor

Inclusion Criteria:

* The patients were aged from 1 to 70 years old (including the cut-off value), and the gender was not limited;
* The expected survival time was more than 12 weeks;
* ECoG score was 0-2;
* One of the following tumor types was confirmed by pathology: osteosarcoma, neuroblastoma, gastric cancer or lung cancer, and the positive rate of cd276 expression in tumor tissue was more than 50% by immunohistochemistry;
* Patients with ineffective standard treatment methods (such as postoperative recurrence, chemotherapy, radiotherapy, and progression after targeted drugs);
* According to RECIST 1.1, there was at least one measurable lesion (the longest diameter of solid lesion ≥ 10 mm, or the short diameter of lymph node lesion ≥ 15 mm);
* The function of main organs was normal (white blood cell count ≥ 3 × 109 / L, neutrophil count ≥ 1.5 × 109 / L, hemoglobin ≥ 8.5g/dl, platelet count ≥ 80 × 109 / L and lymphocyte count at 1 × 109 / L (including) \~ 4 × 109 / L (inclusive);
* The liver and kidney function and cardiopulmonary function meet the following requirements:

  1. Urea and serum creatinine ≤ 1.5 × ULN；
  2. Left ventricular ejection fraction ≥ 50%;
  3. Baseline oxygen saturation ≥ 94%;
  4. Total bilirubin ≤ 1.5 × ULN； ALT and AST ≤ 2.5 × ULN；
* The patient or legal representative can fully understand the significance and risk of this trial and has signed the informed consent.

Exclusion Criteria:

* Patients with history of immune deficiency or autoimmune diseases (including but not limited to rheumatoid arthritis, systemic lupus erythematosus, vasculitis, multiple sclerosis, insulin-dependent diabetes, etc.); Patients with graft-versus-host disease (GVHD) or need immunosuppressive agents;
* There was a history of other second malignancies in 5 years before screening;
* Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) were positive, and the peripheral blood HBV DNA titer was not within the normal reference value; HCV antibody and HCV RNA in peripheral blood were positive; HIV antibody positive patients; Syphilis was positive;
* Severe heart disease: including but not limited to unstable angina pectoris, myocardial infarction (within 6 months before screening), congestive heart failure (NYHA classification ≥ III), severe arrhythmia;
* Unstable systemic diseases judged by researchers: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
* Within 7 days before screening, there were active or uncontrollable infections requiring systemic treatment (except mild urogenital infection and upper respiratory tract infection);
* Pregnant or lactating women, female subjects who plan to conceive within one year after cell transfusion, or male subjects whose partners plan to conceive within one year after cell transfusion;
* Patients who had received car-t therapy or other gene modified cell therapy before screening;
* The subjects who were receiving systemic steroid treatment within 7 days before the screening or who needed long-term systemic steroid treatment (except inhalation or local use) were determined by the researchers;
* The ascites increased gradually after 2 weeks of conservative treatment (such as diuresis, sodium restriction, excluding ascites drainage);
* According to the judgment of the researcher, it does not conform to the situation of cell preparation;
* Other researchers think that it is not suitable for inclusion.