Humanized Mouse Models
Each of our humanized mouse model platforms are available exclusively for application in our tumor studies, and have been characterized with known immune checkpoint inhibitors of clinical relevance, to help you take the next step in evaluating your compound in immuno-oncology. The humanized mice model platforms available are:
- Humanized CD34+ (huCD34) Mouse Models
- Humanized PBMC (huPBMC) Mouse Models
- Knock-in Humanized Mouse Models
Our team can help design appropriate studies and select the best model platform to help you reach your goals. Start by watching the webinar below.
Humanized models allow the use of human tissue, which more closely represents the disease state seen in the clinic. We have validated our humanized mice models for our patient-derived xenograft (PDX) models as well as our human cell line derived xenograft (CDX) portfolio.
Humanized CD34+ (huCD34) Mouse Models
CD34+ humanized mouse models are ideal for long-term oncology studies as they involve stable engraftment of huCD34+ hematopoietic stem cells (HSC), and produce multi-lineage human immune cells that are present up to nine months later.
CD34 Humanized Mouse Models
Figure 1: Diagram of CD34+ humanized mice models for tumor studies.
Severely deficient immune mice are preconditioned by whole body irradiation, followed by intravenous engraftment of human CD34+ cells. Humanized mice carrying human CD45+ cells, including B- and T-cells are ready for tumor cells of PDX implantation 12 to 14 weeks post CD34+ cells engraftment.
Characteristics of the model include:
- Human CD34+ cells engraft stably
- Long-term studies without developing graft vs host disease (GvHD)
- Multi-lineage engraftment
- Display robust T cell maturation
Humanized PBMC (huPBMC) Mouse Models
The PBMC humanized mouse model features more rapid engraftment of human immune cells, providing a cost-effective option for short-term oncology studies. These models are ideal for our tumor studies evaluating compounds for T cell immune modulation.
PBMC Humanized Mouse Models
Figure 2: Diagram of PBMC humanized mice tumor models.
Severely immune-deficient mice are humanized by intravenous or intraperitoneal engraftment of human PBMCs. Human tumor cell are implanted prior or following PBMCs engraftment depending on the tumor growth characteristics of each particular xenograft model.
Characteristics of the model include:
- Short-term, cost-effective studies
- Quick engraftment (from approximately Week 3)
- Ideal for studies requiring mature T cells
PBMC humanized models can develop graft vs host disease (GvHD) three to four weeks post engraftment. The onset of GvHD is PBMC-donor dependent. This humanized model provides a useful tool to evaluate the efficacy of immunosuppressants, cellular therapies, IO therapies, among other therapeutic modalities in the prevention or exacerbation of GvHD.
Knock-in Humanized Mouse Models
Knock-in humanized mouse models are genetically modified animals, in which a murine gene or sequence is replaced by a human counterpart under the regulation of the endogenous promoter. Thus, the expression and signal transduction pathways that regulate the function of that particular protein or enzyme are not altered.
- Humanized CTLA-4 or PD-1 mouse models express chimeric proteins consisting of a humanized extracellular domain that binds directly to clinical grade human antibodies and activates a signal transduction pathway mediated by the murine intracellular portion of the protein. This results in a physiological response in a fully immune competent animal.
- Knock-in humanized mouse models offer a unique research strategy in the immuno-oncology field, as they provide a tool to evaluate the anti-tumor response of immune checkpoint inhibitors directed to human targets in preclinical syngeneic tumor models with a fully functional immune system.
These models can be combined with a variety of tools to enhance your study outcomes, such as:
Are you looking to purchase a humanized mouse model for your own studies? Charles River offers various humanized mice options depending on your location.
Frequently Asked Questions (FAQs) for Humanized Mouse Models
Why use humanized mice in tumor studies?
It is critical to test cancer immunotherapies in an intact immune system; humanizing mice, confirmed by flow cytometry, make this possible. These humanized models allow us to both test the effect of immunotherapies and use human tumor tissue without host rejection. Patient derived xenograft models allow therapies to be tested in a system with real human tissue and preserved tumor heterogeneity.
Which humanized mouse model is the best for my tumor studies?
Due to the complexity of the human immune system, it is important to choose the most appropriate humanized model for your tumor studies. Each model has its advantages, so your choice depends on your study objectives. CD34+ humanized mouse models are good for long-term studies as they maintain stable engraftment; CD45+ cells (mature white blood cells) have been detected in the peripheral blood up to nine months after injection with CD34+ hematopoietic stem cells. PBMC humanized models involve rapid engraftment, so these are suitable for short term studies testing T cell modulation. Humanized knock-in models allow expression of human targets, so syngeneic models can be used to test the response of immune checkpoint inhibitors.
How do CD34+ humanized models differ from other humanized models for tumor study?
CD34+ humanized mouse models are suitable for long-term tumor studies as they maintain steady engraftment. In tumor studies using CD34+ models, activated effector T cells appear to play a role in tumor rejection. While combination therapy improves the number and quality of effector T cells, moderate toxicity is observed. Lack of professional APC (antigen presenting cells) may restrict the overall tumor specific T cell response.
How do PBMC humanized models differ from other humanized models for tumor study?
PBMC humanized mouse models are ideal for short-term tumor studies as they achieve rapid engraftment. Using PBMC models in tumor studies has shown that combination therapy promotes T cell expansion. There is a limited therapeutic window, and the lack of APC may restrict the generation of tumor specific T cells.