Dual-Targeting CAR-NK Cell Therapy for Recurrent/Progressive Glioblastoma and High-Grade Glioma

Ki vehet részt

• Age 18 to 75 years at the time of consent
• Histologically confirmed glioblastoma (WHO grade 4) or diffuse high-grade glioma (WHO grade 3 or 4) that is recurrent or progressive after standard therapy
• Planned clinically indicated tumor resection or stereotactic biopsy (or availability of adequate archived tumor tissue) to support antigen testing and locoregional catheter placement
• Tumor demonstrates expression of at least two of the following antigens above protocol-defined thresholds: IL13Rα2, EGFR (wild-type) and/or EGFRvIII, B7-H3 (CD276)
• Karnofsky Performance Status (KPS) ≥ 60
• Adequate organ function (hematologic, renal, hepatic) as defined by protocol laboratory criteria
• Ability to undergo brain MRI with contrast (unless contraindicated and alternative imaging is permitted)
• Negative pregnancy test for women of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined period after infusion
• Ability to understand and willingness to sign informed consent

Ki nem vehet részt

• Requirement for high-dose systemic corticosteroids (e.g., >4 mg/day dexamethasone equivalent) within 7 days prior to lymphodepletion/infusion (physiologic replacement permitted)
• Active, uncontrolled infection (including uncontrolled bacterial, viral, or fungal infection)
• Known HIV infection with uncontrolled viral load; active hepatitis B or hepatitis C with detectable viral load (unless permitted per protocol)
• Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months
• Diffuse leptomeningeal disease as the only site of disease, or anatomy that precludes safe catheter placement (unless specifically allowed by protocol)
• Uncontrolled seizures despite optimal medical therapy
• Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia) that would increase risk with lymphodepletion or infusion procedures
• Any condition that, in the investigator's judgment, would make the participant unsuitable for the study or could interfere with protocol adherence
• Prior gene-modified cellular therapy (e.g., prior CAR-T/CAR-NK) within 6 months, or prior therapy targeting IL13Rα2, EGFR/EGFRvIII, or B7-H3 where residual engineered cells could confound safety assessments
• Pregnant or breastfeeding