This is a single-center, open, dose-increasing study. For subjects with recurrent glioblastomaIt ,is estimated that about 22 subjects will be enrolled, The main purpose was to evaluate the safety and tolerance of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment of patients with recurrent glioblastoma.The secondary purpose is to preliminarily evaluate the anti-tumor activity of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment of patients with recurrent glioblastoma, and preliminarily evaluate the relationship between the clinical efficacy, safety and pharmacokinetics of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) preparation, as well as their correlation with tumor markers or other potential biomarkers.

This clinical study is an open clinical study, including dose increasing stage and expansion stage. The main objective of the study was to observe the efficacy and safety of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) in the treatment of Glioblastoma (GBM) by local administration (Omaya capsule administration). The study will be divided into the following stages: screening stage, baseline stage, treatment stage, short-term follow-up and long-term follow-up stage.

Inclusion Criteria:

1. 18 ≤ age ≤ 70 years old, gender unlimited;
2. Patients with recurrent glioblastoma confirmed by histology or cytology after surgery and treated with STUPP regimen (TMZ concurrent radiochemotherapy and adjuvant chemotherapy regimen);
3. According to the response assessment in neuro-oncology(RANO) standard, tumor lesions with evaluable or measurable (measurable enhancement lesions are defined as enhancement lesions with clear boundary on CT or MRI, which can be developed on ≥ 2 axial films with a thickness of 5 mm, and the length and diameter of each other are more than 10 mm. If the scanning layer thickness is large, the minimum measurable lesion should be more than 2 times the layer thickness);
4. Clinical pathology (immunohistochemical staining) confirmed the positive expression of EGFRvIII in the tumor;
5. Sufficient peripheral blood can be obtained through vein, and there is no other contraindication for lymphocyte collection; The peripheral blood cells can be collected according to the requirements of cell preparation;
6. KPS score ≥ 70 points;
7. Estimated survival time ≥ 3 months;
8. Subjects must give informed consent to the test before the test, and the written informed consent form shall be signed voluntarily by themselves (or their legal representatives).-

Exclusion Criteria:

1. Those who have received radiotherapy after recurrence;

2. They received immunosuppressive or glucocorticoid treatment within 2 weeks before enrollment;

3. Those who receive live vaccine within 4 weeks before enrollment and/or plan to participate in the trial;

4. He received other chemical drugs except lymphocyte clearance within 2 weeks before enrollment;

5. Not recovered from the adverse events caused by previous anti-tumor treatment before enrollment (according to NCI-CTCAE v5.0, recovered to ≤ 1 level), excluding hair loss and sequelae;

6. Previously received targeted drug therapy, cell therapy, gene therapy or other immunotherapy;

7. Have received organ transplantation in the past;

8. Those who are unable to perform brain MRI examination;

9. Any of the following exceptions occurred in the laboratory inspection:

   1. Blood routine test: absolute neutrophil count (ANC) < 1.5 × 10 ⁹/L, or platelet (PLT) < 80 × 10 ⁹/L, or hemoglobin (HGB) < 100 g/L;
   2. Coagulation function: prothrombin time (PT), or activated partial thromboplastin time (APTT), or INR > 1.5 × ULN；
   3. Liver function: total bilirubin (TBIL)>2 × ULN (upper limit of normal value), or alanine transferase (ALT), aspartate transferase (AST) > 3 × ULN；
   4. Renal function: serum creatinine (Cr) ≥ 1.5 × ULN, or glomerular filtration rate (GFR) < 60ml/min · 1.73m2;
   5. Subjects with active hepatitis B after treatment (HBsAg positive and HBV-DNA more than 1000 copies/ml (200 IU/ml) or higher than the lower detection limit, whichever is higher) are required to receive anti hepatitis B virus treatment during the study treatment; Active hepatitis C subjects (HCV antibody positive and HCV-RNA level higher than the lower limit of detection), human immunodeficiency virus or acquired immunodeficiency syndrome (HIV) related diseases. Note: Hepatocellular carcinoma(HCC) subjects with Hepatitis B virus(HBV) may be included in the study only after the researchers determine that their hepatitis is in a clinical stable state; No HCC subjects undergoing treatment are allowed to be enrolled with HCV;
   6. Cardiac ultrasound: left ventricular ejection fraction Left ventricular ejection fraction(LVEF)<50%;

10. Acute bacterial or fungal infection requiring intravenous antibiotics during cell transfusion;

11. Negligent compensatory heart failure (NYHA grade III and IV), unstable angina pectoris, acute myocardial infarction, persistent and clinically significant arrhythmia occurred within 3 months before enrollment;

12. Those who need to inhale oxygen to maintain blood oxygen saturation above 95% before entering the group and cannot return to normal within 2 weeks;

13. Having other malignant tumors and not being effectively controlled;

14. Have a history of tuberculosis;

15. Those who are known or expected to have allergic reactions or have a history of allergy to any component of the test treatment;

16. Known contrast agent allergy;

17. Have a clear history of mental disorders in the past;

18. Previous history of drug abuse or drug abuse;

19. Pregnant or lactating women, or those who plan to become pregnant during the study period;

20. Women of childbearing age and men with fertility cannot take effective and adequate contraceptive measures (such as intrauterine devices, condoms, spermicidal gel plus condoms, diaphragms, etc.) during the period of receiving the study drug and three months after the end of the study;

21. Those who participated in other clinical trials within 30 days before study enrollment;

22. The investigator judged that it was not suitable to participate in this clinical trial.