PERSONALIZED MULTI-EPITOPE PEPTIDE VACCINE DESIGN TARGETING NOTCH1 MUTATIONS IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (T-ALL): A COMPREHENSIVE IMMUNOINFORMATICS ANALYSIS

Large-scale somatic mutation data from COSMIC v97, GenomePaint (St. Jude Cloud), and TARGET/TCGA (N = 1,392 T-ALL samples) were integrated to identify high-frequency hotspot mutations at exons 26–27. Five MHC class I neoepitopes were predicted and stringently filtered using NetMHCpan-4.1, HLAthena, and NetMHCstabpan against a Vietnamese-prevalent HLA allele panel. A multicomponent vaccine construct was assembled incorporating the molecular adjuvant CTB, two universal T-helper epitopes (P2/P30), three MHC class II helper epitopes from NOTCH1 and RHEB, one linear B-cell epitope from NOTCH1, and a clinically validated modified WT1 epitope (CYTWNQMNL). The construct underwent comprehensive evaluation of physicochemical and immunological properties, 3D structure prediction (AlphaFold2/RoseTTAFold2), molecular docking (AutoDock Vina, PatchDock/FireDock), immune simulation (C-ImmSim), and codon optimization (JCat).