Inclusion Criteria:
To be eligible for participation in this study, individuals must meet the following criteria:
1. Subjects must be able to comprehend and voluntarily sign written informed consent, which includes requirements related to study sample collection.
2. Able to communicate with researchers; Understand and comply with the requirements of the study; Voluntary and able to complete study procedures and follow-up examinations.
3. Be male or female patients aged 18 (including those with borderline age values).
4. Patients with recurrent or progressive high-grade gliomas (WHO grade III-IV) that have been histopathologically or molecularly diagnosed and for which there is either no current standard of care or the standard treatment has proven ineffective (progression of the disease after treatment or intolerance of treatment).
5. At least 1 intracranial measurable lesion according to RANO criteria (well-defined enhancing lesion detected on MRI, diameter \>10 mm).
6. Patient's willingness to undergo surgical maneuvers related to placement of the Ommaya capsule.
7. Karnofsky functional status ≥ 60.
8. Be expected to survive for at least 3 months.
9. No serious hematologic (no adjuncts such as EPO, G-CSF, or GM-CSF within 14 days prior to the first dose and no blood transfusions for at least 7 days), hepatic, or renal function abnormalities consistent with the following laboratory test results:
systems Laboratory test values routine blood test Absolute neutrophil count（ANC） ≥1.5×109/L blood platelet（PLT） ≥100×109/L hemoglobin（HGB） ≥90g/L gallbladder serum creatinine（Cr） ≤1.5×Upper limit of normal range（ULN） creatinine clearance（Ccr）（To be calculated only if creatinine \> 1.5 x ULN） ≥50mL/min（Based on the Cockcroft-Gault formula） liver total bilirubin（TBIL） ≤1.5×ULN glutamic pyruvic transaminase（ALT） aspartate transaminase（AST） ≤2.5×ULN Alkaline phosphatase（ALP） ≤2.5×ULN coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5×ULN Partially activated thromboplastin time（APTT） ≤1.5×ULN 10.Male or female subjects of childbearing potential use effective contraception during treatment and for 6 months after dosing.
Exclusion Criteria:
1. Inability to perform an MRI for any reason.
2. focal point under the curtain.
3. Prior history of encephalitis, multiple sclerosis, or other central nervous system infection (unless resolved).
4. Patients with a previous diagnosis of any other malignancy within 5 years prior to the first dose, except for malignancies with a low risk of metastasis and risk of death (5-year survival \> 90%), such as adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, and other carcinomas in situ.
5. Females of childbearing age who have a positive pregnancy test or are lactating.
6. Individuals with allergies (defined as ≥2 drug allergies) or hypersensitivity to similar products or excipients.
7. Those who have received smallpox vaccination and experienced severe systemic reactions or side effects.
8. Patients who have previously received lysosomal virus, stem cell, or gene therapy products.
9. Individuals using other investigational drugs or participating in clinical trials of other drugs within 28 days prior to the first dose (except for those who did not receive the test drug).
10. Those who have undergone antitumor therapy, including radiation therapy (except palliative radiotherapy), chemotherapy, biotherapy, endocrine therapy, and immunotherapy within 28 days prior to the first administration of the drug.
11. Individuals who have undergone surgery or interventional therapy (excluding tumor biopsy, puncture, Ommaya capsule etc.).
12. Individuals who have been treated with systemic corticosteroids (at a dose equivalent to \>10 mg dexamethasone /day) or other immunosuppressive medications within 28 days prior to the first dose, or who are currently taking antiviral medications (Mainly sensitive to poxviruses), enrollment is permitted under the following cases:
1. short-term (≤7 days) use of corticosteroids for prophylaxis or treatment of non-autoimmune allergic diseases is permitted;
2. the use of topical topical or inhaled glucocorticoids is permitted;.
13. A history of severe cardiovascular disease, including but not limited to:
1. A history of severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias, degree II-III AV block requiring clinical intervention;
2. Acute coronary syndrome, congestive heart failure, aortic coarctation, stroke, or other grade or greater cardiovascular event within 6 months prior to the first dose;
3. New York Heart Association (NYHA) \> Class II heart failure or left ventricular ejection fraction (LVEF) \<50%; heart rate-corrected baseline QTcF intervals \>450msec (men) and \>470msec (women) using the Fridericia formula; any factor that increases the risk of QTc prolongation or the risk of cardiac arrhythmias, such as heart failure, hypokalemia , congenital long QT syndrome, family history of long QT syndrome, or use of any concomitant medication known to prolong the QT interval；
4. Clinically uncontrolled hypertension (blood pressure uncontrolled at \< 160 mmHg systolic and \< 100 mmHg diastolic after standard antihypertensive treatment).
14. Recent Grade 3 or greater bleeding event within 6 months prior to the first use of study drug, or who have current \> Grade 2 bleeding, or hemangioma/vascular malformation, or tumor stroke, tumor invasion of a blood vessel, or active peptic ulcer, or esophageal varices judged by the investigator to be at significant risk for bleeding.
15. Those with a history of severe hemoptysis.
16. Patients with uncontrolled or severe diseases, including but not limited to persistent or active infections requiring antibiotic therapy.
17. .Subjects with active or prior history of autoimmune diseases with potential for recurrence (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.) or at high risk (e.g., patients who have undergone organ transplantation requiring immunosuppressive therapy) are not eligible for enrollment. However, enrollment is permitted for subjects with:
1. type 1 diabetes mellitus that is stabilized on a fixed dose of insulin;
2. autoimmune hypothyroidism or Hashimoto's thyroiditis that requires only hormone replacement therapy；
3. Individuals with a history of exfoliative skin conditions requiring systemic therapy (e.g., eczema or atopic dermatitis) are also excluded.
18. Persons who are positive for human immunodeficiency virus (HIV) antibodies.
19. Persons who have active hepatitis B (HBV)/hepatitis C (HCV) infection are not eligible for enrollment. However, subjects with a previous history of hepatitis C but negative HCV RNA at screening may be enrolled, and those who are HBsAg positive but have HBV DNA \<500 IU/ml or below the lower limit of detection at the study center may also be enrolled. Subjects with primary liver cancer and HBV DNA \<1000 IU/ml may be enrolled as well.
20. Patients with documented psychiatric illnesses or disorders that may impact adherence to the trial protocol.
21. Patients with malignant tumors that may require antitumor therapy other than the investigational drug GC001.
22. Patients who, as determined by the investigator, are unsuitable for participation in the study.
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