This is a single-center, open-label, dose-escalation, multiple-dose investigator-initiated trial (IIT). The trial aims to evaluate the safety and tolerability of autologous dendritic cell injection sensitized with tumor neoantigens (YS247) in participants with recurrent or progressive glioblastoma, as well as to assess preliminary efficacy and pharmacodynamic characteristics. The study consists of four phases: screening, baseline, treatment, and follow-up. During the treatment phase, participants will be assigned to three dose groups (low, medium, and high) and enrolled following the "3+3" dose-escalation principle. YS247 will be administered subcutaneously once every 2 weeks for a total of 8 consecutive doses.

A total of 9 to 18 participants are planned to be enrolled in this study. A dose-escalation design will be adopted following the 3+3 escalation principle, and the injection dose of the study drug YS247 is preset at three dose levels (low, medium, high) as specified below, with 3 to 6 participants planned to be enrolled in each dose level group. An adaptive trial design will be implemented, where the number of enrolled participants in each group will be adjusted based on the actual clinical study results

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.