CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.

主要终点：Incidence of dose-limiting toxicities (DLTs) · Incidence of dose-limiting toxicities (DLTs) after CAR-NK infusion (CTCAE v5.0; CRS and ICANS grading). · 28 Days；Maximum tolerated dose (MTD) · 12 months
次要终点：Objective response rate (ORR)；Disease control rate (DCR)；Progression-free survival (PFS)；Overall survival (OS)

• IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK · EXPERIMENTAL · Participants whose tumors meet eligibility thresholds for IL13Rα2 and EGFR (and/or EGFRvIII) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and EGFR/EGFRvIII.
• IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK · EXPERIMENTAL · Participants whose tumors meet eligibility thresholds for IL13Rα2 and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and B7-H3.
• EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK · EXPERIMENTAL · Participants whose tumors meet eligibility thresholds for EGFR (and/or EGFRvIII) and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing EGFR/EGFRvIII and B7-H3.

This is a draft, ClinicalTrials.gov-style example record for a first-in-human Phase 1 study evaluating locoregional administration of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in adults with recurrent or progressive glioblastoma (GBM) or other high-grade glioma (HGG). Participants will undergo tumor antigen profiling for IL13Rα2, EGFR/EGFRvIII, and B7-H3 (CD276). Based on this assessment, each participant will receive the most suitable dual-target CAR construct to reduce antigen-escape risk.