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

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Requirement for high-dose systemic corticosteroids (e.g., \>4 mg/day dexamethasone equivalent) within 7 days prior to lymphodepletion/infusion (physiologic replacement permitted).
* 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.
* 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.
* Pregnant or breastfeeding.
* Any condition that, in the investigator's judgment, would make the participant unsuitable for the study or could interfere with protocol adherence.