Abstract 6965: Utilizing a humanized CD8 mouse model for non-clinical studies of cancer immunotherapy

Abstract 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. Citation Format: Hannah Horton, Zhi Zhang, Zhiyuan Shen, Zhenlan Niu, Xiaofei Zhou. Utilizing a humanized CD8 mouse model for non-clinical studies of cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6965.