PBMC Humanized Mouse Models for Immuno-Oncology
A rapid, T cell-driven humanized mouse platform for evaluating checkpoint inhibitors, T-cell engagers, CD3 engagers, and bispecific antibodies in oncology research.
A Rapid and Practical Platform for Immuno-Oncology Research
Immuno-oncology drug development requires preclinical models that combine human immune relevance, experimental efficiency, and robust efficacy readouts. Cyagen’s PBMC-humanized NKG in vivo system is established by engrafting human peripheral blood mononuclear cells (PBMCs) into severely immunodeficient mice, NKG, enabling rapid human immune cell reconstitution with a predominantly T cell-driven profile. This platform is particularly suitable for short-window in vivo efficacy studies of checkpoint inhibitors, T-cell engagers, CD3 engagers, and next-generation antibody therapeutics. With integrated model development, in vivo pharmacology, and downstream analytical support, Cyagen provides an end-to-end CRO solution for oncology studies utilizing human immune system-reconstituted PBMC mouse models.
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Our huPBMC-NKG models are constructed by transplanting human peripheral blood mononuclear cells (PBMC) into severe immunodeficient NKG mice. This model offers a highly efficient platform for evaluating immuno-oncology therapies, particularly those relying on T-cell responses.
Key Features of the huPBMC-NKG Platform
Rapid human immune reconstitution
Human CD45+ leukocytes in peripheral blood reach more than 25%
by around 3 weeks post-engraftment.
T cell-predominant immune profile
The reconstituted human immune compartment is composed
predominantly of T cells, supporting T cell-centered pharmacology studies.
Fast turnaround for efficacy studies
The model supports short-window study designs suitable for
rapid in vivo assessment.
Cost-effective alternative to HSC-based HIS models
Compared with HSC humanized systems, PBMC humanization offers
a faster and more practical route for selected study goals.
Relevant Mouse Model
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Human Immune Reconstitution Comparison
Highlight: huPBMC-NKG demonstrates superior and stable human CD45+ engraftment compared to other
standard immunodeficient strains.
Figure 1. Comparison of hCD45 reconstitution in huPBMC-NKG mice
and two publicly available NKG similar strains using donor 1 and donor 2. Under the tested
conditions, huPBMC-NKG showed reconstitution comparable to Strain B and stronger than
Strain
C.
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Cyagen supports in vivo efficacy studies in PBMC humanized NKG models for multiple
classes of immuno-oncology therapeutics, including checkpoint inhibitors, T-cell engagers, CD3
engagers, and bispecific antibodies.
Representative In Vivo Pharmacology Studies & Applications
| Drug | Modality | Tumor Cell Line | Key Endpoints | Representative Result | Research Application | Action |
|---|---|---|---|---|---|---|
| in vivo CAR-T | BCMA CAR mRNA-LNP | 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 | |
| Keytruda | PD-1 inhibitor | HCT116 | TGI; T-cell exhaustion analysis | TGI reached 30%; reduced T-cell exhaustion | PD-1 inhibitor efficacy studies | |
| Tecentriq | PD-L1 inhibitor | NCI-H358 | TGI; body weight monitoring | Superior TGI and less body weight loss in NKG mice | PD-L1 antibody evaluation | |
| Blincyto | T-cell engager | Luci-EGFP-Nalm-6 | Bioluminescence signal; TGI | Lower tumor signal; TGI = 70% | T-cell engager efficacy studies | |
| Tarlatamab | CD3 engager | SHP-77 | Tumor growth inhibition; dose response | Dose-dependent tumor inhibition | CD3 engager studies | |
| Ivonescimab (AK112) | PD-1/VEGF bispecific antibody | H358 | Tumor suppression vs monotherapies | Superior efficacy over PD-1 or VEGF monotherapy | Bispecific antibody efficacy studies |
A Rapid Platform for In Vivo CAR-T Evaluation
In vivo CAR technologies are a next-generation strategy for cell therapy. Our huPBMC-NKG
model contains a high proportion of human T cells, providing an ideal and rapid platform for
evaluating in vivo CAR efficacy in hematologic malignancies.
Evaluating in vivo BCMA CAR-T in huPBMC-NKG mouse model
This study evaluated an LNP-delivered in vivo CAR targeting BCMA in a multiple myeloma model
established by subcutaneous implantation of BCMA-expressing NCI-H929 cells in
huPBMC-NKG mice. Antitumor activity, body weight, and in vivo CAR expression in human immune
cell subsets were assessed to characterize both efficacy and pharmacodynamic response.
Figure 1. Immune humanization level in huPBMC-NKG mice. (A)
The proportion of human CD45 cells; (B) the proportion of human T cells.
Figure 2. An LNP-delivered in vivo CAR targeting BCMA was
tested in a multiple myeloma model established by subcutaneous implantation of NCI-H929
cells with BCMA expression in huPBMC-NKG mice. (A) Tumor volume; (B) Body weight; (C)
Body weight change; (D) BCMA-CAR+ % in hCD45 cells; (E) BCMA-CAR+ % in hCD8 cells. Tumor
growth inhibition reached 62% compared with the control group, after five doses of
treatment. CAR-positive cells accounted for 42% of human CD8⁺ T cells 24 hours after the
first dose, indicating efficient CAR expression in human CD8 T cells.
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To support mechanism-relevant interpretation of in vivo efficacy data, Cyagen
provides integrated in vitro and ex vivo analytical services for PBMC humanized oncology
studies. These readouts help characterize immune reconstitution, treatment response, and
pharmacology-related changes across blood and tumor samples.
Immune Reconstitution Assessment
Quantification of human CD45+ leukocytes and human immune cell
subsets in peripheral blood.
Tumor Immune Profiling
Analysis of tumor-infiltrating human T cells and
treatment-related changes in immune status, including exhaustion-associated
phenotypes where applicable.
In Vivo Imaging Readouts
Bioluminescence-based monitoring for relevant tumor models
such as Luci-EGFP-Nalm-6.
General Pharmacology Endpoints
Tumor volume measurement, body weight monitoring, and
efficacy-related endpoint interpretation.
Case Studies
Our models undergo rigorous validation to ensure they are robust and reliable tools for your research.
Explore our case studies below, which highlight the successful characterization of our humanized genetic
models and our expertise in conducting preclinical drug efficacy studies.
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Why Partner with Cyagen?
Comprehensive Humanized Model
Cyagen offers integrated capabilities in humanized mouse model development, PBMC engraftment, and in vivo study execution, enabling researchers to move efficiently from model selection to pharmacology evaluation.
Mechanism-Relevant Study Design
Our team supports study designs aligned with immuno-oncology mechanisms, including T-cell-mediated responses, immune checkpoint evaluation, and human immune cell–tumor interactions, helping generate more biologically informative data.
Integrated Readout Capabilities
From tumor growth assessment to immune profiling, flow cytometry, and histopathology, Cyagen provides end-to-end analytical support to help researchers interpret efficacy and mechanism with greater clarity.
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