Human Immune System (HIS) Mouse Models for Immuno-Oncology
Bridge the translational gap in IO drug development. Cyagen delivers a proprietary platform of stable HIS mouse models paired with multidimensional in vivo profiling to accurately assess the efficacy of your immunotherapies.
A Rapid and Practical Platform for Immuno-Oncology Research
Successful immuno-oncology preclinical studies often require more than T-cell reconstitution alone. For mechanisms involving antigen presentation, innate immune participation, ADCC, myeloid biology, or tumor microenvironment remodeling, broader reconstruction of the human immune system can be critical. Cyagen’s huHSC-NKG-ProF platform is a human hematopoietic stem cell (HSC)-based model developed to support fuller human immune system reconstitution, generating lymphoid and multiple myeloid cell populations in vivo.
Compared with faster but more T cell-skewed humanization approaches, this platform is designed for studies that require a more diversified immune context, including T cells, B cells, NK cells, dendritic cells, monocytes/macrophages, and selected immunosuppressive populations. In oncology, the platform has been applied in tumor vaccine evaluation, ADCC-related studies, tumor immune infiltration analysis, and translational research supported by published literature. Related HSC-humanized NKG models have also been used for T-cell engager studies.
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Cyagen’s huHSC-NKG-ProF model is established through human HSC engraftment in immunodeficient NKG mice and is designed to achieve broad human immune reconstitution in vivo. The platform supports the development of both lymphoid and multiple myeloid cell populations in vivo, enabling evaluation of therapies that rely on complex immune cross-talk, such as ADCC, antigen-presentation-associated responses, and tumor microenvironment interactions.
Relevant Mouse Model
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Key Features of the huHSC-NKG-ProF Platform
Broad human immune reconstitution
The model supports reconstitution of T cells, B cells, NK
cells, and multiple myeloid populations, including dendritic cells, monocytes,
macrophages, and granulocyte-lineage cells.
Physiologically Relevant T & NK Cell Profiles
Spleen CD4/CD8 ratio is approximately 2:1 (matching human
physiological levels), and NK cells reach nearly 20% in the spleen.
Reconstitution of myeloid and selected immunoregulatory
compartments
Myeloid cells account for about 25% of the splenic human
immune compartment, with successful reconstitution of immunosuppressive populations
like Tregs and MDSCs.
Model Comparison
| huHSC-NKG | huHSC-NKG-ProF | NKG similar HIS | |
|---|---|---|---|
| Humanization ratio | 40-60% | 40-60% | 40-60% |
| T cell ratio | 20-50% Without Treg |
20-50% With Treg |
20-50% With Treg |
| NK cell ratio | Peripheral blood 1% | Peripheral blood 10% Spleen 20% | Peripheral blood 1% |
| Myeloid cell ratio | Peripheral blood： Monocyte 2-4％, decline after 10 weeks Very few other types of myeloid cells |
Peripheral blood 5% Spleen 10-20% |
Peripheral blood 5% |
| Myeloid subtype (In proportion to white blood cells) | Peripheral blood： Monocyte 2-4％, decline after 10 weeks Very few other types of myeloid cells |
Peripheral blood： Monocyte 2-4%, cDC 2% Spleen： Monocyte 10%, cDC 2% MDSC 1.5%, Macrophage 4% Marrow： cDC 7% |
Peripheral blood： Monocyte 2-4% The DC, MDSC, and Macrophage data are not applicable. |
| Applications | T cell focused applications | Tumor vaccine, ADCC, T cell applications | T cell focused applications |
Note: Data shown are representative platform-level characteristics summarized from internal
model evaluation materials.
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In Vivo Pharmacology Services Enabled by HIS Models
Cyagen supports in vivo efficacy studies using huHSC-NKG-ProF and related HIS platforms for
multiple classes of immuno-oncology therapeutics. Depending on the mechanism of action and tumor
model characteristics, these studies can be designed to evaluate treatment activity driven by T
cells, NK cells, dendritic cells, or broader tumor-infiltrating immune populations.
| Application | Modality / Study Type | Tumor Model | Key Readouts | Representative Finding | Research Relevance | Action |
|---|---|---|---|---|---|---|
| Cancer Vaccine | Antigen-specific immunotherapy | NCI-H929 | TGI；BCMA-CAR+ % in hCD8+ T cells | TGI reached 62%; BCMA-CAR expression in > 40% of hCD8+ T cells. | in vivo CAR-T efficacy studies | |
| ADCC | Anti-CD20 monoclonal antibody | Raji lymphoma | Tumor growth inhibition | Rituximab showed significant therapeutic activity | NK-cell-dependent mechanism studies | |
| T-cell Engager | GPC3/CD3 bispecific antibody | Hepatocellular carcinoma PDX | TGI | TGI reached 72% after 21 days in huHSC-NKG model | T-cell engager efficacy evaluation |
Featured Case Study — Exploratory In Vivo CD19 CAR-T Evaluation
This exploratory study assessed the in vivo activity of CD19 CAR-T cells in
huHSC-NKG-ProF mice. Human immune reconstitution profiles were evaluated across donor
groups, and treatment-associated changes in human B-cell abundance were subsequently
monitored in vivo.
Figure 1. Immune humanization profile in huHSC-NKG-ProF mice. Panels A–E
show the proportions of human leukocytes, T cells, B cells, NK cells, and myeloid
cells across three donor groups in huHSC-NKG-ProF mice (N = 10).
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To support mechanism-informed interpretation of in vivo results, Cyagen
provides integrated immune profiling and downstream analytical services for HIS-based studies.
These readouts help characterize human immune reconstitution, treatment-related immune
activation, and tumor microenvironment remodeling across peripheral and tumor tissues.
Comprehensive Immune Reconstitution Assessment
Flow cytometry-based quantification of major human immune subsets, including T cells, B cells,
NK cells, dendritic cells, monocytes, and selected suppressive populations, across peripheral
blood, spleen, and bone marrow.
High-Resolution Tumor Immune Profiling (TILs)
Deep characterization of tumor-infiltrating lymphocytes and myeloid cells.We support immune
phenotyping and tumor immune infiltration profiling to help inform model selection and study
design.
Tumor Immune Infiltration
Profiling in ProF Mice
Figure 1. The tumor microenvironment (TME) varies drastically between cell lines in
ProF mice. For instance, epidermal carcinoma cell line A431 tumors exhibit diverse
infiltration (60% T cells, 5% NK cells, 25% myeloid cells), whereas melanoma cell
line A375 tumors are almost exclusively infiltrated by T cells.
Mechanism-Relevant Functional Readouts
Assessment of antigen-specific T-cell activation, cytokine-related signals, and
immune
phenotype changes associated with treatment response.
Autoimmune Disease Extensions
Application of HIS models beyond oncology, including DSS-induced IBD models and
Pristane-induced SLE models, complete with histological and autoantibody readouts.
IBD Mouse Model Induced by DSS
Figure 1. Histopathology findings in DSS-treated HIS mice showed
intestinal ulceration, epithelial and glandular damage, inflammatory-cell
infiltration, and submucosal edema, indicating feasibility for inflammatory bowel
disease-related exploratory studies.
Case Studies
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Published Evidence Supporting Translational Utility
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Why Partner with Cyagen?
Broad Human Immune Reconstitution Expertise
Cyagen supports advanced HIS model development and study execution with platforms designed to enable broader human immune reconstitution, including lymphoid and myeloid compartments for mechanism-relevant in vivo research.
Application-Oriented Study Design
Our HIS models are aligned with diverse translational use cases, including tumor vaccine studies, ADCC evaluation, T-cell engager assessment, tumor immune infiltration profiling, and broader immuno-oncology pharmacology studies.
Integrated In Vivo and Immune Profiling Capabilities
From model establishment and efficacy studies to flow cytometry, tumor immune profiling, and histopathology, Cyagen provides end-to-end support to help researchers generate interpretable and decision-enabling data.
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