e20624 Background: To establish and validate a shared neoantigen peptide library based on NSCLC hotspot mutations for efficient personalized neoantigen identification and to explore its application in combination therapy for EGFR-TKI-resistant patients. Methods: A peptide library was constructed from hotspot mutations in key NSCLC genes (EGFR, TP53,KRAS,CTNNB1,CDKN2A,HER-2 ) and common Chinese HLA types using NetMHCpan for epitope prediction. Tumor mutations were identified via NGS/RT-PCR, and HLA genotyping was performed. PBMCs from 51 matched patients were stimulated with corresponding peptides. T-cell activation (IFN-γ, CD137) and cytokine profiles were assessed by ELISPOT/flow cytometry, and neoantigen-specific CTL cytotoxicity was confirmed. A clinical trial evaluated the safety and efficacy of the shared neoantigen vaccine combined with chemotherapy and PD-1 blockade in advanced, TKI-resistant NSCLC. Results: The library comprised 44 high-affinity peptides. Immunogenicity testing identified 29 immunogenic peptides inducing IFN-γ/CD137 expression and specific target cell lysis. In 7 enrolled TKI-resistant patients, the combination therapy resulted in 1 complete response, 3 partial responses, and 3 stable disease (DCR = 100%). Median PFS was 7.5 months and median OS was 23.6 months. Vaccine-related adverse events were manageable (e.g., injection-site reactions, fatigue). Conclusions: The validated shared neoantigen peptide library provides a novel platform for rapid neoantigen discovery and represents a safe and effective combination therapy strategy for NSCLC patients with acquired TKI resistance. Clinical trial information: NCT06095934 .
Chen et al. (Thu,) studied this question.