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Immunotoxicity

Immunotoxicity in Humanized Immune System Mouse Model

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Immunotoxicity refers to unintended adverse effects of therapeutics on the immune system, including immunosuppression, hypersensitivity reactions, and excessive immune activation such as cytokine storm. These risks are especially critical when developing T cell engagers, CAR-T cells, and other immune-modulating therapies, where overstimulation of the immune system can lead to severe or life-threatening events.

TransCure bioServices offers a CD34+ humanized immune system mouse model designed to detect and evaluate human-specific immunotoxicity in vivo, particularly well-suited for evaluating the safety profiles of T cell engagers, CAR-T therapies, and bi-specific antibodies.

Main characteristics

  • Global Clinical Score

    Animals are closely monitored throughout the study for any clinical signs, including body weight loss, changes in breathing, diarrhea, altered movement, and fur texture. These observations help detect early signs of immunotoxicity or distress, ensuring timely intervention and accurate evaluation of treatment-related effects.

  • Body Temperature

    In the context of cytokine storm, monitoring body temperature is a key readout. A notable drop in body temperature is often observed, serving as an early indicator of systemic immune overactivation. Regular temperature tracking helps detect severe immune responses and supports the evaluation of safety profiles for immunotherapies.

  • Cytokine Release

    To assess cytokine release, we perform Cytometric Bead Array (CBA) analysis on peripheral blood samples. This allows for quantitative monitoring of key cytokines involved in cytokine storm, including TNF-α, IL-6, IL-10, IL-2, and IFN-γ. These biomarkers provide valuable insights into the intensity and profile of the immune response triggered by immunotherapies.

  • Blood immunophenotyping

    Peripheral blood is also used for immunophenotyping by flow cytometry, enabling the analysis of immune cell depletion and activation markers such as OX40, PD-1, CD25, and CD69. This provides detailed insights into T cell activation dynamics and helps evaluate the immunostimulatory or immunosuppressive effects of the tested compounds.

  • Necropsy

    At study termination, key organs such as the liver, spleen, heart, and lungs are collected for macroscopic evaluation and weight measurement, providing an initial assessment of organ-specific toxicity or inflammation. Tissues may then be processed for H&E staining, allowing detailed histopathological analysis to detect cellular damage, immune infiltration, or structural changes linked to treatment-related effects.

Applications

The right mouse model for your research experimentation

  • Human Immune System Mouse Model

    Evaluate both the efficacy and immunotoxicity of your lead candidate using a fully reconstituted human immune system, generated by engrafting CD34+ hematopoietic stem cells into highly immunodeficient mice.

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Know everything about 
the CD34+ humanized mouse

  • How do you generate humanized mice?
    Humanized Immune System mice are generated by engrafting CD34+ hematopoietic stem cells (HSCs) into highly immunodeficient NCG mice, enabling the development of a functional human immune system, including T cells, B cells, monocytes, DC, NK cells and other key immune subsets
  • Do we need to further boost the humanized mice ?
    To gain a comprehensive view of human immune responses, enhancing the differentiation of myeloid cells and NK cells is essential. Boosting these lineages makes the model more physiologically complete, enabling more accurate evaluation of innate and adaptive immune interactions.

You have more questions ?

If you have further questions or would like to discuss how our humanized immune system mouse model can be tailored to your specific research needs, our scientific team is here to help. We’re committed to providing clear, responsive support and working closely with you to design studies that align with your objectives. Don’t hesitate to reach out - we’re always happy to share our expertise and explore solutions together.

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