利用人源化CD8小鼠模型开展癌症免疫治疗的非临床研究

Background: The CD8 is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen-presenting cell in the context of class I MHC molecules. The coreceptor functions as either a homodimer composed of two alpha chains or as a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. Cytotoxic CD8+ T cells of the adaptive immune system are the most powerful effectors in the anticancer immune response and constitute the backbone of cancer immunotherapy. Methods: To more accurately evaluate the efficacy of drugs targeting the human immune system, Biocytogen generated a CD8 humanized mouse model that expresses the human CD8 protein. Results: Protein expression analysis of this novel humanized CD8 mouse strain indicates that the model exclusively expresses human CD8 protein without mouse CD8 protein detection. Immunoprofilling analysis demonstrates that the proportions of various immune cell subsets remain unaffected following CD8 humanization. This model possesses normal T cell immunogenic function, as confirmed by OVA-induced immune responses. In vivo efficacy studies show that CD8+ T cells in this model can effectively kill tumor cells. These findings indicate that the CD8 mouse model serves as a powerful research tool, which can not only be used to study and validate the in vivo efficacy of anti-human CD8 agonistic antibodies, but also to investigate CD8-targeting drugs or their synergistic effects with other therapies (such as checkpoint inhibitors). Conclusion: We have established a promising preclinical research model using CD8 humanized mice. This model serves as a powerful preclinical tool for assessing the efficacy of CD8+ T cell-based immunotherapies, including immune checkpoint blockers, neoantigen vaccines, CAR-T, and TCR-T cell therapies.