Abstract
<title>Abstract</title> <p>Therapeutic vaccines for non-small cell lung cancer (NSCLC) are almost invariably designed against global HLA supertypes, yet the immunogenetics of Southeast Asian patients diverges substantially from the largely European allele sets underlying them. We report CRUISER, a dual-arm vaccine restricted to a Vietnamese-specific panel of 12 HLA class I alleles and 13 class II specificities. The T-cell arm is a 273-residue recombinant protein carrying eight KRAS and EGFR neoepitopes fused to the chemokine XCL1, which targets the construct to XCR1-positive conventional type 1 dendritic cells, the subset specialised in cross-presentation. The antibody arm comprises four disulfide-cyclised peptides drawn from the ligand-binding faces of PD-L1 and VEGFR2, selected on structural rather than antigenicity criteria. Seventeen of 92 candidate epitopes survived a four-layer safety and potency cascade. Combined population coverage reached 73.35% in Vietnam against 46.78% worldwide and 41.23% in Europe, quantifying the gain conferred by population restriction. Critically, triplicate 100 ns molecular dynamics simulations benchmarked against a free XCL1:XCR1 positive control showed that fusion preserves receptor engagement: the fusion complex matched the free chemokine in MM-PBSA interaction energy, maintained more interface hydrogen bonds, and distorted neither the XCL1 core nor the receptor. All findings are computational predictions requiring experimental validation.</p>