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Evaluation of drug efficacy using immunohumanized mice

Invivocue, for which we act as an agent, offers contract drug efficacy testing using humanized immune system mice (HiMice). A variety of disease models using humanized mice are available.

For inquiries or requests regarding testing with Invivocue, please feel free to contact Lunapas Toxicology and Pathology Laboratory.

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About Invivocue

Invivocue is a Singapore-based CRO specializing in the creation and efficacy testing of humanized mice. We undertake various efficacy tests using our own humanized mice.

Humanized Mice:

Human Immune System Mice (HiMice): Humanized mice in which human immune cells can stably engraft and survive for long periods.
Human Liver Chimeric Mice (HepMice): Chimeric mice in which human liver cells have been stably reconstructed.
Dual Humanized Mice: Mice in which the human immune system and human stem cells have been simultaneously reconstructed.

Humanized mouse disease models:

Cancer-bearing models (CDX, PDX)
Graft-versus-host disease model (GvHD)
Acute Respiratory Distress Syndrome Model (ARDS)
Inflammatory bowel disease model (IBD)
Non-alcoholic steatohepatitis (NASH) model
Systemic lupus erythematosus model (SLE)
Cytokine syndrome (CRS)

Facility Overview

In vivo efficacy studies:

Disease model (mouse)

Recreating the human immunotumor microenvironment in HiMice models has become the most advanced and promising platform for evaluating the efficacy and safety of immunotherapies. Invivocue constructs tumor models using patient-derived xenografts (PDX) or cell line-derived xenografts (CDX). Scientific evidence has shown that human tumor growth in HiMice progresses significantly in the presence of the human immune system, exhibiting marked immune checkpoint expression compared to conventional nude mouse, immunodeficient mouse, and syngeneic mouse models. Past research findings better reflect the clinical situation.

Graft-versus-host disease (GvHD) develops after allogeneic hematopoietic stem cell transplantation (HSCT) when donor T cells trigger an immune response against host tissue, presenting a wide range of clinical symptoms from mild skin rashes to life-threatening multi-organ failure. While HSCT is one of the most effective treatments for hematological malignancies, approximately half of patients who undergo HSCT develop GvHD complications, with a mortality rate of 15–30% (Dignan et al., 2012). Immunosuppressants reduce the risk of graft rejection, but an effective treatment for GvHD has yet to be established. Invivocue supports researchers by providing a standard xenogeneic GvHD model in which adult peripheral blood mononuclear cells (PBMCs) are transplanted into immunodeficient mice. This model is a valuable tool for elucidating the pathophysiology of GvHD and testing new therapies.

High-level biosafety containment laboratories and human ACE2-expressing mouse strains necessary for infectious disease research are difficult to access. Furthermore, many immunomodulatory agents, such as anakinra and tocilizumab, are human-specific and do not cross-react with mouse receptors, so there is a need to model acute respiratory distress syndrome (ARDS) in humanized mice as an alternative model for pulmonary fibrosis, inflammation, and cytokine release syndrome (CRS). These acute clinical symptoms are commonly seen in COVID-19 patients and can be reproduced in humanized mice using ARDS-inducing substances such as lipopolysaccharide (LPS), bleomycin, and influenza A (H1N1) virus.

Inflammatory bowel disease (IBD), primarily ulcerative colitis and Crohn's disease, is an inflammatory disease of the gastrointestinal tract caused by multiple factors, including abnormalities in the gut microbiota, dysregulation of the immune response, and environmental factors. While the pathogenesis of IBD is not fully understood, immunological factors such as cytokines (e.g., IL-1β, IL-6, IL-18, TNFα, IL-17), TH17 cells, innate lymphoid cells, and monocytes/macrophages are thought to be involved. Therefore, therapies targeting cytokines and immune cells may be effective in treating IBD. Invivocue can create an acute IBD model by allowing humanized mice to freely ingest dextran sulfate sodium (DSS) dissolved in drinking water for 8-10 days, or by rectally administering 2,4,6-trinitrobenzenesulfonic acid (TNBS). Clinical progression of colitis is evaluated using body weight, stool condition, and disease activity index (DAI) scores.

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder characterized by the accumulation of excess lipids in liver cells. Persistent inflammation can progress to severe liver fibrosis and even cancer, leading to a condition called non-alcoholic steatohepatitis (NASH). Conventional NAFLD/NASH models are typically genetically modified or chemically induced, lacking a connection to the human liver and immune system. In contrast, we successfully reproduced the characteristics of NAFLD/NASH using only a high-fat, high-carbohydrate (HFHC) diet in HiMice. This allows for detailed study of the interaction between human immune cells and liver cells during NASH progression, enabling the identification of new immunotherapy targets and evaluation of anti-fibrotic drugs.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by numerous antinuclear antibodies, systemic inflammation, and lymphopenia resulting from immune system dysfunction. Invivocue has successfully replicated most of the clinical and immunological features of SLE in B-cell enhanced HiMice via single-dose pristane induction. The cytokine, autoantibody, and T-cell/B-cell responses in this SLE model are human-specific. Therefore, this model provides a unique in vivo platform for disease pathophysiological studies, immunotherapy target identification, and drug evaluation.

Invivocue website