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

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.

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