The application of HIS mouse models

Humanized immune system (HIS) mice have revolutionized biomedical research, serving as indispensable tools for advancing personalized medicine and translating immune-based therapies into clinical practice. By engrafting human immune cells or tissues into immunodeficient mice, these models provide a powerful platform to study human-specific immune responses in vivo. Below, we explore the key applications of HIS mice across various fields:

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1. Immune Oncology

HIS mice have become critical for developing and testing cancer immunotherapies. Models such as human PBMC-engrafted mice and CD34+ engrafted mice are widely used to evaluate immune checkpoint inhibitors (e.g., anti-PD-1, anti-CTLA-4), T cell engagers, and adoptive cell therapies like CAR-T. These models enable researchers to study tumor-immune interactions, assess therapeutic efficacy, and identify mechanisms of resistance.

2. Autoimmune Diseases

Humanized mice, particularly PBMC-engrafted models, have provided fundamental insights into the mechanisms of autoimmune diseases such as rheumatoid arthritis, lupus, and multiple sclerosis. These models allow researchers to study human T cell and B cell responses, evaluate the efficacy of immune-modulating therapies, and investigate the role of cytokines in disease progression.

3. Human-Specific Infectious Diseases

BLT mice (Bone Marrow, Liver, Thymus) are uniquely valuable for studying human-specific infectious diseases, including HIV, hepatitis, and tuberculosis. These models support the development of HLA-educated T cells and antigen-specific immune responses, making them ideal for investigating pathogen-host interactions, testing antiviral therapies, and developing novel treatment strategies.

4. Vaccine Development

HIS mice play a pivotal role in vaccine research, particularly for complex pathogens like HIV, malaria, and SARS-CoV-2. BLT mice and CD34+ engrafted mice are used to evaluate vaccine efficacy, study mucosal immunity, and optimize adjuvants. These models provide critical preclinical data to guide the development of next-generation vaccines.

5. Cytotoxic Responses: CRS and IrAEs

Humanized mice are also instrumental in studying cytotoxic responses associated with immunotherapies, such as cytokine release syndrome (CRS) and immune-related adverse events (IrAEs). For example, PBMC-engrafted mice are used to model CRS, a life-threatening complication of CAR-T cell therapy, and to test interventions like anti-IL-6 therapies. Similarly, these models help researchers understand and mitigate IrAEs caused by immune checkpoint inhibitors.