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

Exploratory Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247) in Patients With Recurrent or Progressive Glioblastoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Biological: Neoantigen DC Vaccine (YS247) for Glioblastoma

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaomin Liu, Chief Physician; Phone Number: 13502068866; Email: liuxiaomintj@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoantigen DC Vaccine (YS247) for Glioblastoma; 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.

Biological: Neoantigen DC Vaccine (YS247) for Glioblastoma; Exploratory Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247) in Patients with Recurrent or Progressive Glioblastoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Treatment Tolerability	Evaluate the incidence of treatment-related adverse events (TRAEs) of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247, Beijing YSCell Biotech Co., Ltd., abbreviated as YS) in patients with recurrent or progressive glioblastoma based on CTCAE v5.0, to assess the safety and tolerability of the product.	From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days)
Maximum Tolerated Dose (MTD) and Recommended Expanded Dose(RP2D)	Based on the incidence of dose-limiting toxicities (DLTs), establish the MTD of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247) for patients with recurrent or progressive glioblastoma, and define the RP2D. DLT is defined as any study drug-related AE (per CTCAE 5.0) or laboratory abnormality occurring from first dose to 4 weeks post-dose, unrelated to disease progression, comorbidity, or concomitant medication, including: CTCAE Grade 3 non-hematological toxicity lasting >7 days.; Immune-related Grade 3 pneumonia, recurrent Grade 2 pneumonia.; Other Grade 3 irAE not recovering to ≤Grade 2 in 3 days or ≤Grade 1 in 14 days with intervention.; CTCAE Grade 4 non-hematological toxicity.; CTCAE Grade 4 hematological toxicity lasting >7 days.; CTCAE Grade 5 toxicity of any type.; Any unexpected toxicity requiring treatment termination per investigator/sponsor judgment.	From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	Determined per RANO criteria via radiographic evaluation of intracranial tumor lesions.	From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days)
Duration of Response (DoR)	Calculated per RANO criteria based on serial radiographic tumor lesion assessments.	From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days)
the safe and efficacious dose range	Characterized based on the incidence of dose-limiting toxicities (DLTs) and anti-tumor response data assessed per RANO criteria	From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days)
Objective Response Rate (ORR)	Determined per Response Assessment in Neuro-Oncology (RANO criteria) via radiographic evaluation of intracranial tumor lesions.	From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neoantigen-specific T cell count	Peripheral blood mononuclear cells (PBMCs) collected at scheduled visits to quantify neoantigen-specific T cell counts by IFN-γ ELISpot assay.	From subject enrollment to the end of the 8th treatment cycle (each treatment cycle lasts 14 days)
T cell activation phenotypes	Peripheral blood mononuclear cells (PBMCs) collected at scheduled visits to detect activation phenotypes of neoantigen-specific T cells via multi-color flow cytometry.	From subject enrollment to the end of the 8th treatment cycle (each treatment cycle lasts 14 days)
Cytokine secretion level of neoantigen-specific T cells	Peripheral blood plasma collected at scheduled visits to measure cytokine secretion of neoantigen-specific T cells using ELISA assay.	From subject enrollment to the end of the 8th treatment cycle (each treatment cycle lasts 14 days)
T cell receptor clonotype diversity and clonal expansion	Peripheral blood mononuclear cells (PBMCs) collected at scheduled visits to analyze neoantigen-specific T cell receptor clonotype diversity and clonal expansion by full-length TCR sequencing.	From subject enrollment to the end of the 8th treatment cycle (each treatment cycle lasts 14 days)

Collaborators and Investigators

• Sponsor: Huanhu Hospital Affiliated to Tianjin Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): May 30, 2028

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Glioblastoma; Tumor neoantigen; Immune cell therapy; Dendritic cell (DC)
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 202603241156000268775

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No