Exploratory Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247, Beijing YSCell Biotech Co., Ltd. [Abbreviated as YS])in Patients With Recurrent or Progressive Glioblastoma

Inclusion Criteria:

1. Age 18-75 years (inclusive), any gender.
2. Histologically confirmed GBM (WHO Grade IV).
3. Recurrence/progression confirmed by MRI after standard therapy (surgery, Stupp protocol); ≥1 measurable lesion (max diameter ≥1.0 cm) on contrast-enhanced MRI per RANO criteria.
4. KPS score ≥60, expected survival ≥6 months.
5. ECOG score 0-2.
6. Bridging therapy allowed during sample preparation; washout ≥7 days or 5 half-lives (whichever longer) before initial treatment.
7. Radiotherapy completed ≥8 weeks before study drug initiation.
8. Toxicity from prior anti-tumor therapy recovered to CTCAE V5.0 Grade 1 or below (except alopecia).

9. Adequate organ function:

   • ANC ≥1.5×10⁹/L, ALC ≥0.8×10⁹/L, HGB ≥90 g/L, PLT ≥100×10⁹/L
   • AST/ALT ≤2.5×ULN, TBIL ≤2.5×ULN, ALB ≥3 g/dL, ALP ≤2.5×ULN
   • INR/APTT ≤1.5×ULN (except therapeutic anticoagulation)
   • Cr ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault)
   • Normal ECG, LVEF ≥50% (ECHO)
   • Resting SpO₂ >92% without oxygen
10. Adequate venous access for PBMC collection, no contraindications.
11. Sufficient tumor and blood samples for NGS via resection or biopsy.
12. Negative serum pregnancy test (fertile females); effective contraception throughout screening, study, and 6 months after last dose for fertile participants/partners.
13. Compliance with study procedures and follow-up.
14. Voluntary participation and signed informed consent.

Exclusion Criteria:

1. Any other active malignancy.
2. Participation in another clinical trial within 4 weeks before enrollment.
3. Prior gene transfer therapy.
4. Concurrent anti-tumor therapy within 4 weeks before initial treatment (except allowed bridging); blood transfusion, EPO, G-CSF, or GM-CSF within 14 days before PBMC apheresis.
5. Live virus/recombinant vaccine within 4 weeks before first treatment; expected need for live attenuated vaccine within 6 months after last dose.
6. Severe allergy or hypersensitivity.
7. MRI contrast contraindications (pacemaker, pump, contrast allergy).
8. Positive HIV, HBV, HCV, or TP.
9. Primary/secondary immunodeficiency or autoimmune disease (SLE, RA, IBD, autoimmune thyroid disease, autoimmune hepatitis, MS, vasculitis, glomerulonephritis, psoriasis, uncontrolled asthma).
10. Severe infection within 1 month before treatment, uncontrolled infection, or antibiotics in the past week (except prophylaxis).
11. Systemic immunosuppressive therapy within 30 days before initial treatment (short-term use allowed with sponsor approval; permitted: inhaled steroids, mineralocorticoids, low-dose steroids ≤10 mg/day prednisone equivalent).
12. Uncontrolled systemic disease (NYHA III/IV heart failure, unstable angina, MI, cirrhosis, renal failure, severe lung disease, hematological/gastrointestinal/organ failure, diabetes, uncontrolled hypertension).
13. ICD-11 psychiatric/neurological disorders (epilepsy, schizophrenia, dementia, addiction) per investigator judgment.
14. Clinically significant bleeding within 3 months or bleeding diathesis; arterial/venous thromboembolism within 6 months (TIA, stroke, DVT, PE).
15. Irreversible electrolyte imbalance.
16. Anti-tumor therapy before apheresis: cytotoxic within 14 days; investigational within 28 days; immunomodulator within 7 days; targeted within 28 days.
17. Pregnant or lactating female.
18. Any other condition deemed unsuitable by the investigator.