Inclusion Criteria:
1. Voluntarily signs written informed consent.
2. 18 to 65 years of age, inclusive, male or female.
3. Newly diagnosed postoperative glioblastoma confirmed by histopathology or molecular pathology as WHO CNS grade 4 glioblastoma, IDH-wildtype, according to the 2021 WHO Classification of Central Nervous System Tumors.
4. Tumor tissue positive for CD44 or CD133 antigen expression by immunohistochemistry, defined as CD44 or CD133 staining positive in at least 1% of tumor cells, regardless of staining intensity.
5. At least one preoperative measurable lesion meeting RANO 2.0 criteria outside the radiation field, with the longest diameter of the measurable lesion no greater than 3 cm by imaging assessment.
6. No prior radiotherapy and no prior treatment with temozolomide, bevacizumab, or other anti-tumor therapy for glioblastoma.
7. Confirmed by the investigator to be suitable for Ommaya reservoir implantation.
8. Adequate venous access for peripheral blood mononuclear cell collection.
9. Karnofsky Performance Status (KPS) score of at least 70 within 1 week before PBMC collection and within 4 days before Tris-CAR-T cell infusion.
10. Expected survival of at least 3 months.
11. Adequate bone marrow, hepatic, renal, coagulation, and oxygenation function within 1 week before PBMC collection and within 1 week before Tris-CAR-T cell infusion, including HGB at least 100 g/L, WBC at least 3.5 × 10\^9/L, ANC at least 1.5 × 10\^9/L, PLT at least 100 × 10\^9/L, lymphocyte count greater than 1 × 10\^9/L, ALT and AST no more than 2.5 × ULN, TBIL no more than 1.5 × ULN, creatinine no more than 1.5 × ULN, PT or INR no more than 1.5 × ULN, APTT no more than 1.5 × ULN, and resting oxygen saturation without oxygen at least 95%.
12. Left ventricular ejection fraction greater than 50% and electrocardiogram QTcF no more than 480 msec within 14 days before PBMC collection and within 14 days before Tris-CAR-T cell infusion.
13. For female participants of childbearing potential, negative pregnancy tests within 2 weeks before PBMC collection and within 1 week before the first CAR-T cell infusion. Participants of childbearing potential, male or female, must agree to use effective medical contraception from screening through 2 years after the last cell infusion.
14. Willing and able to comply with protocol-specified visits, study treatment, laboratory tests, and other study-related requirements.
Exclusion Criteria:
1. Autologous CAR-T cell manufacturing cannot be completed or the CAR-T cell product does not meet clinical use requirements.
2. Highly allergic constitution, history of severe allergy, or allergy to related cell products.
3. Receipt of approved or investigational anti-tumor therapy within 2 weeks before PBMC collection or within 5 half-lives of the therapy, whichever is longer, including but not limited to chemotherapy, radiotherapy, surgery other than diagnostic surgery, targeted therapy, cell infusion therapy, hormone therapy other than hormone replacement therapy, or traditional Chinese medicine with a clear anti-tumor indication; a 1-week washout is acceptable for traditional Chinese medicine.
4. Severe clinical infection greater than Grade 2 by NCI CTCAE v6.0 within 2 weeks, uncontrolled active infection, or unexplained fever before PBMC collection or Tris-CAR-T cell infusion.
5. Prior anti-tumor treatment-related adverse reactions have not recovered to Grade 1 or lower by NCI CTCAE v6.0, except alopecia, skin pigmentation, leukoplakia, or other findings judged by the investigator to pose no safety risk.
6. Tumor lesion metastasis to the brainstem or spinal cord.
7. Serious neurological diseases other than the brain tumor, such as meningitis, encephalitis, myelitis or demyelinating disease, myasthenic syndrome or myasthenia gravis, amyotrophic lateral sclerosis, spinal muscular atrophy, nerve palsy, or uncontrolled epilepsy.
8. Myocardial infarction, coronary artery bypass grafting, coronary angioplasty, coronary stent implantation, pulmonary embolism, new arterial or deep venous thrombosis, stroke, or transient ischemic attack within 6 months, excluding brain tumor bleeding or brain tumor surgery-related bleeding.
9. Heart failure NYHA class 2 or higher, myocarditis, cardiomyopathy, pericarditis, cardiac valve morphological abnormality Grade 2 or higher, unstable coronary heart disease, poorly controlled hypertension with systolic blood pressure at least 150 mmHg or diastolic blood pressure at least 100 mmHg, or severe arrhythmia or conduction abnormality requiring medication.
10. Severe respiratory disease requiring treatment, such as pneumonia, chronic bronchitis, asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, interstitial lung disease, or respiratory failure.
11. Hepatitis requiring treatment, uncontrolled or unstable liver function impairment, or diabetes mellitus not controlled with medication.
12. Severe urinary system disease or abnormality requiring treatment, such as proteinuria, glomerulonephritis, or renal function abnormality.
13. Primary immunodeficiency disease, autoimmune disease requiring medication, such as Crohn disease, ulcerative colitis, rheumatoid arthritis, or systemic lupus erythematosus, or history of neurological autoimmune disease such as multiple sclerosis or Parkinson disease.
14. Receiving or requiring long-term immunosuppressive therapy, except physiologic systemic corticosteroid replacement equivalent to prednisone 10 mg/day or less, short-term corticosteroids for no more than 7 days for prevention or treatment of non-autoimmune allergic disease, or topical, intra-articular, intranasal, inhaled, or other local glucocorticoids.
15. Prior allogeneic bone marrow transplantation or organ transplantation, or awaiting organ transplantation.
16. HBsAg positive with HBV DNA positive, HCV antibody positive with HCV RNA positive, Treponema pallidum antibody positive, or HIV antibody positive.
17. Prior gene therapy or cell therapy.
18. Pregnant or lactating female.
19. History of malignancy other than glioma within 5 years, except adequately treated carcinoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer, or stage I cervical cancer judged by the investigator to have very low risk of recurrence.
20. Any other disease, abnormal test result, psychiatric factor, or social factor that may affect compliance with protocol procedures, place the participant at high risk when receiving the investigational product, or interfere with interpretation of study results, making the participant unsuitable for this clinical study in the investigator's judgment.
