Myeloid-enhanced HIS mouse model comparisons

Traditional HIS mouse models harbor immune systems primarily composed of lymphocytes, including T cells and B cells. Consequently, these models have emerged as robust in vivo platforms for the development of clinical therapeutics targeting lymphoid cells, including PD-1 blockade antibodies and other immune checkpoint inhibitors (ICIs), T cell engagers, and adoptive immunotherapies (i.e. CAR-T). However, due to limited homology between certain human and murine cytokines, these popular HIS mouse models (BRG, NOG, NSG) exhibit impaired human myeloid cell differentiation, restricting their translational use in studies of innovative immunity-based immunotherapies, such as efforts to modulate human-specific antibody-dependent cellular phagocytosis (ADCP), analyses of myeloid-derived suppressor cells (MDSCs), and research focused on antigen-specific immune responses. To overcome this obstacle, human cytokines (including M-CSF, GM-CSF, IL-3, and SCF) were genetically engineered into immunodeficient mouse models and expressed at different levels using different techniques. The below table highlights the characteristics of several myeloid-enhanced HIS mouse models.