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CAR-T Cell Therapy Animal Models

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

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.

Model Selection

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.

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.

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

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.

CAR-T Cell Therapy Animal Models

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

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

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