Inclusion Criteria:
1. Adequate compliance, ability to comprehend the clinical trial, and provision of written informed consent.
2. Male or female, aged ≥16 years.
3. Histologically or cytologically confirmed WHO Grade III or IV glioma harboring one or more of the following mutations: H3.3K27M, H3.1K27M, H3.3G34R, BRAF V600E, PIK3CA H1047R, IDH1 R132H, or EGFRvIII.
4. Recurrent or progressive high-grade glioma, defined as a CNS WHO Grade 3-4 glioma confirmed by post-surgical histopathology, with documented recurrence or progression per RANO criteria on MRI following standard therapy (radiotherapy plus temozolomide chemotherapy).
5. Life expectancy ≥3 months.
6. Karnofsky Performance Status (KPS) ≥50. For subjects with spinal cord lesions, functional deficits due to paralysis will not be considered in the KPS assessment.
7. Absence of significant bone marrow, cardiac, pulmonary, or renal dysfunction, defined as:
1. Hematologic (without transfusion or hematopoietic growth factor support within 14 days):
* Absolute Neutrophil Count (ANC) ≥1.5 × 10⁹/L
* Platelet count (PLT) ≥100 × 10⁹/L
* Hemoglobin (HGB) ≥90 g/L
2. Hepatic Function:
* Alanine Aminotransferase (ALT) ≤2.5 × Upper Limit of Normal (ULN)
* Aspartate Aminotransferase (AST) ≤2.5 × ULN
* Total Bilirubin (TBIL) ≤1.5 × ULN
3. Renal Function:
\* Serum creatinine ≤1.5 × ULN OR estimated creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula)
4. Coagulation:
* Activated Partial Thromboplastin Time (APTT) ≤1.5 × ULN
* International Normalized Ratio (INR) ≤1.5 × ULN
5. Other:
* Left Ventricular Ejection Fraction (LVEF) ≥50% without clinically significant pericardial effusion on echocardiogram
* No clinically significant electrocardiogram (ECG) abnormalities
* Baseline oxygen saturation \>92% on room air
8. Adequate immune function, defined as receiving dexamethasone ≤2 mg/day within the 3 days prior to screening without severe lymphopenia.
9. Negative pregnancy test for women of childbearing potential (WOCBP); non-pregnant and non-lactating females; both male and female participants must agree to use highly effective contraception and have no plan for pregnancy within 6 months after study entry.
Exclusion Criteria:
1. History of other malignancies within the past 5 years (except appropriately treated carcinoma in situ of the cervix or non-melanoma skin cancer).
2. History of hypersensitivity to chemotherapy agents or radiosensitizers used for central nervous system or head and neck cancers.
3. History of severe allergic reactions to vaccines or any components of the investigational product.
4. Positive serology for:
* Human Immunodeficiency Virus (HIV) antibody
* Hepatitis C Virus (HCV) antibody with detectable HCV RNA
* Hepatitis B Surface Antigen (HBsAg) with HBV DNA ≥2000 IU/mL
* Treponema pallidum (TP) antibody with a positive confirmatory test (e.g., RPR/TPPA)
5. Active, uncontrolled infection, active tuberculosis, or active immunosuppressive disease.
6. Any concurrent non-malignant illness or psychiatric condition that would preclude safe protocol participation; uncontrolled cardiovascular disease (e.g., coronary artery disease, angina, myocardial infarction, significant arrhythmias).
7. Inability or unwillingness to provide informed consent or participate voluntarily.
8. Concurrent participation in another interventional clinical trial or participation within 3 months prior to screening.
9. Severe infection or signs/symptoms of active infection within 2 weeks prior to the first dose of the investigational product.
10. Administration of a live-attenuated vaccine within 4 weeks prior to the first dose.
11. History of solid organ or hematopoietic stem cell transplantation.
12. Any other condition that, in the opinion of the investigator, would jeopardize the subject's safety or compliance with the study protocol.
