Substantial genetic discrepancies exist between the major histocompatibility complex (MHC) systems of animals and the human leukocyte antigen (HLA) system. The utilization of HLA humanized mouse model systems constitutes a superior methodology for examining fundamental mechanisms associated with HLA-A-related vaccine development and HLA-A-restricted immune responses against diseases such as infections and cancers in humans.

To study bothin vitroandin vivothe requirements for shaping an effective T cell response against clinically relevant cancer targets such as NY-ESO-1, WT1 and other newly discovered targets, Biocytogen generated a C57BL/6 background HLA-A2.1 humanized mouse model that is restricted to the human HLA-A2. This humanized mouse model was utilized to evaluate immune responses to a variety of cancer peptide and mRNA vaccines, including analyses of immune cell populations, cytokine production, andin vivoanti-tumor efficacy.

Immunoprofiling analysis of this novel humanized HLA-A2.1 mouse strain revealed that the introduction of the HLA-A2.1 gene significantly influences the immune cell composition in these humanized mice. Following vaccination with various cancer-specific epitopes, HLA-A2.1-restricted, epitope-specific cytotoxic T lymphocytes (CTLs) were induced in the B-HLA-A2.1 mouse model. Furthermore, we established an mRNA vaccination treatment model in B-HLA-A2.1 mice, demonstrating a synergistic antitumor effect when combined with the mRNA vaccine. These findings indicate that the B-HLA-A2.1 mouse model serves as a powerful research tool, not only for investigating HLA-A2.1-restricted CTL responses but also for the preclinical evaluation of vaccines.

We have established a promising preclinical research model using HLA-A2.1 humanized mice. This model could accelerate the identification of novel HLA-A2.1-restricted epitopes and facilitate vaccine development, while also supporting the study of HLA-A2.1-restricted responses against cancers in humans.