We prospectively collected 36 paired cerebrospinal fluid (CSF) and serum (SE) samples from 3 recurrent high-grade GBM patients (overall survival > 12 months) at baseline (Day 0) and on post-CAR-T treatment days 1-5. Comprehensive untargeted proteomic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). We characterized inter-sample proteomic variations through proteomic approaches, elucidated exploratory proteomic changes observed in patients receiving CAR-T therapy, and conducted systematic functional annotation.