Abstract 3537: Development and validation of humanized HLA-A11.1 mouse model for preclinical evaluation of novel peptide vaccines

Abstract The Major Histocompatibility Complex (MHC) is responsible for presenting diverse antigenic peptides and initiating T cell-mediated immune responses. Given the significant genetic differences between animal MHC systems and the human leukocyte antigen (HLA) system, HLA humanized mouse models offer an efficient in vivo system for HLA-A-related vaccine development and for studying HLA-A-restricted response mechanisms in humans. In this study, we present a novel B-HLA-A11.1 mouse model and have thoroughly investigated its phenotypic and immunological attributes. Our findings indicate that the blood routine and biochemistry of B-HLA-A11.1 mice are comparable to those of wild-type mice, suggesting that the humanization of HLA-A11.1 does not adversely alter blood cell composition or morphology, nor does it affect the health status of organs such as the heart, liver, or kidneys. Collectively, these data demonstrate that B-HLA-A11.1 mice develope normally and do not exhibit any evidence of spontaneous pathology due to the humanization of HLA-A11.1. To gain a deeper understanding of the role of MHC molecules, we extended our research using a humanized mouse model to assess immune responses against various cancer target peptides. In summary, our data indicate that humanized HLA-A11.1 mice provide a powerful preclinical model for in vivo/ex vivo evaluation of novel peptide and mRNA vaccines. Citation Format: James Jin, Zhenlan Niu, Ying Zhao, Shuaiqiang Zhang, Zhi Zhang, Hui Xu. Development and validation of humanized HLA-A11.1 mouse model for preclinical evaluation of novel peptide vaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3537.