CAR-T And CAR-NK Cell based Efficacy Evaluation Service in Mouse Tumor Models

Chimeric antigen receptor (CAR)-engineered T cells have demonstrated remarkable results in many hematological malignancies. In addition to CAR-T, CAR-Natural Killer (NK) cell therapy has recently attracted attention with higher feasibility and better cytotoxicity. As of June 2023, there are six approved CAR-T products, and many more in the pipeline of clinical development However, the success of CAR-immune cell therapeutics in solid tumors is challenged by the tumor antigen heterogeneity, impaired transport and infiltration of CAR-immune cells, and suppression of the tumor microenvironment. Fortunately, promising results were observed when combining CAR-based cell therapies with other drugs such as immune checkpoint inhibitors.

Preclinical assessment of CAR-T and CAR-NK cell function, including direct tumor destruction, cytokine production, CAR-immune cell persistence, and therapy-related tumor microenvironment changes, is typically performed in different types of animal models. Creative Biolabs provides immunocompromised and immunocompetent models for functional assessment of CAR-immune cell products, as well as expert insights to design and plan treatment strategies using these models.

Our Capabilities that Support CAR-immune Cell Research

Fig. 1 Murine models of CAR-T therapies. Human cells are depicted
in aqua and mouse cells in pink. (Duncan et al. 2022)

Efficacy studies

• Immune-compromised (xenograft) models
• NOD-scid-IL2rg null based system with full immune defects.
• Validated human cell line-derived xenograft (CDX) covering 17 tumor types.
• Patient-derived xenograft (PDX) models.
  a. Covering the 10 most common cancer types.
  b. Well-annotated with clinical information.
  c. Drug-induced resistant models.
  d. Relapsed and recurrent models with genetic profiling.
• Immune-competent models
• Humanized mouse models
  a. hPBMC/hHSC immunodeficient mice+CDX/PDX.
  b. hPBMC model with delayed GvHD response.
  c. Customized immunodeficient models for improved reconstitution of human immune system.
• Syngeneic tumor models
  a. C57BL/6, BALB/c, and FVB background.
  b. Orthotopic models are available for 8 common cancers.
  c. 15 cancer types with well-characterized responses.
• Transgenic mouse models
  a. Pure C57BL/6 genetic background.
  b. Human antigen-expressing murine tumor cell lines.
  c. Humanized immune checkpoint/cytokine mice for the combination therapy.
• Preclinical functional evaluation
• Genomic, phenotypic, and immune profiling.
• Tumor growth inhibition.
• Survival.
• Whole animal imaging-Biodistribution.

Preclinical safety evaluation

• Cytokine-driven toxicities.
• Hematological analysis.
• Pathological examination.
• Animal clinic observation.

Creative Biolabs believes that the field of CAR-based cell therapies is very promising and will lead to validated and personalized therapeutic options in the future. Therefore, we also offer one-stop CAR-T and CAR-NK therapeutic development services, specializing in high-affinity scFv generation, CAR design and construction, as well as in vitro CAR-T/NK assays.

Questions, solutions, quotes-contact us!

Reference

1. Duncan BB, Dunbar CE, Ishii K. Applying a clinical lens to animal models of CAR-T cell therapies. Mol Ther Methods Clin Dev. 2022;27:17-31.

For Research Use Only.