TH-CAR-027 for Grade 4 Gliomas

Inclusion Criteria: * 1\. Voluntarily participate in the clinical trial; fully understand and are informed about this study and sign the informed consent form; willing and able to comply with and complete all trial procedures. 2\. Male or female patients aged ≥18 years and ≤75 years. 3. Disease Status: Diagnosis of Grade 4 glioma as defined by the 2021 WHO Classification of Tumors of the Central Nervous System, including but not limited to glioblastoma, Grade 4 astrocytoma, and diffuse hemispheric glioma. Subjects must have experienced relapse or progression following standard therapy and are unsuitable for or refuse further surgical resection. Subjects with specific genetic mutations (e.g., NTRK gene fusion or BRAF V600E mutation) must have progressed after receiving corresponding targeted therapy to be eligible. Documentation of relapse/progression must include imaging (MRI or PET) or histopathological confirmation. 4\. B7-H3 Expression: ≥30% positivity for B7-H3 molecule in primary/relapsed tumor tissue by pathological testing. B7-H3 positivity is defined as: the percentage of B7-H3-positive tumor cells among total viable tumor cells in non-necrotic tumor tissue areas ≥30%. 5\. Karnofsky Performance Status (KPS) score ≥60, or Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 6\. Adequate venous access for peripheral blood mononuclear cell (PBMC) collection. 7\. Left ventricular ejection fraction (LVEF) ≥40% by cardiac ultrasound within one month prior to screening. 8\. Resting oxygen saturation ≥95% while breathing room air. 9. Laboratory tests must meet the following criteria within the specified timeframe prior to screening: 1. Hematological Function: Absolute neutrophil count (ANC)≥1.5×10\^9/L, hemoglobin ≥90 g/L, platelet count≥100×10\^9/L, absolute lymphocyte count≥0.15×10\^9/L. No transfusion,granulocyte (macrophage)colony-stimulating factor, recombinant human erythropoietin, recombinant human thrombopoietin, thrombopoietin receptor agonist, recombinant human interleukin-11, or other supportive therapy within 14 days prior to the test. 2. Liver Function: Total bilirubin≤1.5×upper limit of normal (ULN) (except for patients with Gilbert's syndrome characterized by persistent or recurrent unconjugated hyperbilirubinemia in the absence of hemolysis or hepatic pathology); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST)≤2.5×ULN. 3. Renal Function: Serum creatinine ≤1.5×ULN. 4. Coagulation: Prothrombin time (PT) or activated partial thromboplastin time (aPTT) or international normalized ratio (INR) ≤1.5 ×ULN, in the absence of therapeutic anticoagulation. 10\. Female subjects of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. Female subjects of childbearing potential must use highly effective contraception from the start of the trial until 6 months after the last dose of study treatment. Sexually active males, who have not undergone vasectomy, must agree to use barrier contraception from the start of the trial until 6 months after the last dose of study treatment. Exclusion Criteria: Subjects with a known history of severe allergy to any component of the investigational product. Pregnant or lactating women. Body weight \<40 kg. Viral Infections: <!-- --> 1. Seropositivity for HIV antibody or positive serological test for Treponema pallidum (syphilis). 2. Hepatitis B surface antigen (HBsAg) positivity with peripheral blood HBV DNA levels above the upper limit of normal. 3. Hepatitis C virus (HCV) antibody positivity with detectable peripheral blood HCV RNA. Medical History and Concurrent Conditions: <!-- --> 1. Having undergone carmustine wafer implantation surgery within the past 6 months. 2. Known or suspected active autoimmune diseases, including but not limited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc. 3. Current requirement for systemic immunosuppressive therapy or, in the investigator's judgment, a need for long-term immunosuppressant use during the study period. Intermittent use of topical, inhaled, or intranasal corticosteroids is allowed. 4. Uncontrolled psychiatric disorders. Or subjects with a medical or psychiatric history that, in the investigator's opinion, could increase the risk associated with study participation or administration of the study drug, or could interfere with the interpretation of results. 5. Toxicities from prior anticancer therapy have not recovered to ≤ Grade 1 per CTCAE version 5.0 (except for alopecia and other events deemed tolerable by the investigator). 6. Participation in another interventional clinical trial within the past 1 month. 7. Prior treatment with any CAR-T therapy or other gene therapy. 8. Any severe or poorly controlled medical condition that, in the investigator's opinion, may increase the risk associated with study participation or study drug administration, or impair the subject's ability to receive the investigational product. This includes, but is not limited to, cardiovascular/cerebrovascular diseases, renal insufficiency, pulmonary embolism, coagulopathy or requirement for long-term anticoagulation therapy, active or uncontrolled infection requiring systemic treatment. 9. History or presence of other malignancies within the past 3 years, except for adequately treated non-melanoma skin cancer or carcinoma in situ (e.g., cervical, bladder, breast).