What are CAR-T cells?

CAR T cells, or chimeric antigen receptor T cells, are a type of genetically engineered immune cell that targets cancer cells in a patient's body. They are modified T cells extracted from a patient's blood and reprogrammed with CAR molecules that allow them to recognize and attack cancer cells. Once infused back into the patient, the CAR-T cells multiply and actively seek out and destroy cancer cells.

What is a chimeric antigen receptor?

A chimeric antigen receptor (CAR) is a receptor protein artificially engineered to attach to the surface of immune cells . It consists of an extracellular domain that binds to specific antigens on cancer cells, and an intracellular domain that activates the immune cell to kill the targeted cancer cell. CARs are engineered in the laboratory and can be used in immunotherapy to treat cancer by enhancing the immune system's ability to destroy cancer cells.

How are CAR-T cells made?

CAR T cells are made by collecting T cells from a patient's blood and genetically engineering them to express a chimeric antigen receptor (CAR) that recognizes and binds to a specific antigen on the cancer cell's surface. The engineered CAR-T cells are expanded in the lab and then infused back into the patient. Once inside, the CAR-T cells locate and bind to cancer cells, triggering an immune response that destroys the cancer cells.

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CAR-T Cell Therapy Animal Model Development Services

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All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Background Animal Models Platform Capabilities Highlights & Advantages Related Sections

The ideal CAR-T evaluation models are the combination of mice hosting both the human immune system and patient derived tumors. These novel models called "humanized patient-derived xenograft (PDX) model", expressing a human immune system, possess a distinct advantage over other PDX in immunodeficiency mice. Engrafting these humanized mice with human tumors is the future of the preclinical therapeutic development of CAR-T treatment evaluation.

The most useful models for CAR-T research include:

Engraftment of CAR-T in tumor-bearing immunocompromised mice (eg NSG, NCG mice). This model can be used to test human CAR-T therapy and can be used to evaluate the activity against human tumor cell lines (CDX) or patient-derived tumors (PDX).
Engraftment of CAR-T in immunocompromised mice humanized with CD34 hematopoietic stem cells (HSC) or human peripheral blood mononuclear cells (PBMC). This model can evaluate the activity of CAR-T in the presence of human immune cells, thereby increasing its clinical relevance. However, these models are expensive and may be affected by the development of graft-versus-host disease and HLA.
Engraftment of murine CAR-T into a host with complete immunity. The safety of CAR-T therapy can be evaluated in mice with homologous murine tumors or non-tumor-bearing mice.

To use humanized mice effectively and ensure that you use the correct model to answer your specific questions, you need to fully understand the existence and potency of different human immune cell populations in each model. The figure below summarizes the key differences between hPBMC and hCD34 humanized mouse models：

CAR-T Cell Therapy Animal Models

Easy to establish
Enables short to mid-term studies requiring human T cells
Strong effector and memory T cell function
T cell-driven GvHD
Recall responses of human cell donors
Poor myeloid cell engraftment
Lethal xenogeneic GvHD

Applicable to multiple hematopoietic lineages
Primary immune responses
Long-term lifespan
A functional immune system
No donor cell immune reactivity towards host
T cell restricted to murine MHC

Animal Models for CAR-T Cell Therapy

Creative Biolabs has established a preclinical platform for CAR-T cell therapy evaluation which enables us to answer all your preclinical CAR-T questions through our series of translation models. Currently, we provide numerous types of mouse models featuring more complete immune reconstitutions for customers to choose from. Here are some of our mouse models for reference, if you have other needs, please fell free to contact our technical team.

What can you do with Hu-NSG PDX models?

Monitor CAR-T distribution in vivo
Determine CAR-T persistency
Monitor Cytokine Release Syndromes

Other Available Animal Models

NHP Models for assessing immuno-safety (early toxicity ) of CAR-T therapies

NSG-Based PDX Platform Capabilities

Our NSG mouse models have a higher degree of immunodeficiency. It lacks NK cells while lacking T cells and B cells, and innate immunity is compromised. The NSG model is very suitable for human tumor cell transplantation (CDX), human tumor tissue transplantation (PDX), human peripheral blood mononuclear cell (PBMC), and human hematopoietic stem cell (CD34+HSC) transplantation for immune reconstruction. NCG has a long-life cycle, >89 weeks, which is good for long-term transplantation and pharmacodynamic evaluation.

We use patient-derived xenotransplantation (PDX) models to study population diversity, truly mimic the heterogeneity of human diseases and immunotherapy responses, and enhance the transformative value of CAR-T. PDX is a highly predictable model that can preserve the heterogeneous pathological and genetic characteristics of the original patient's tumor and provide a translatable response. Our collection of more than 2,500 well-characterized PDX models provide a wide range of CAR-T cell therapy targets.

hu-ngs-pdx-models

Highlights & Advantages

Easy Establishment
Our CAR-T cell therapy animal models are straightforward to establish.
Versatility
Enables short to mid-term studies requiring human T cells and is applicable to multiple hematopoietic lineages.
Strong Immune Responses
Models exhibit strong effector and memory T cell function, primary immune responses, and recall responses of human cell donors.
Functional Immune System
Provides a long-term lifespan and a functional immune system with no donor cell immune reactivity towards the host.
Predictive Value
PDX models preserve the heterogeneous pathological and genetic characteristics of the original patient's tumor, offering a highly translatable response.
Extended Evaluation
The NCG model's long-life cycle allows for long-term transplantation and pharmacodynamic evaluation.
Clinical Relevance
Engraftment of CAR-T in humanized mice models ensures clinical relevance by evaluating the activity of CAR-T in the presence of human immune cells.
Specialized Models
Availability of various humanized mouse models tailored to specific research needs.

For more detailed information, please feel free to contact us or directly sent us an inquiry.