Inflammation Models

When our immune system is inappropriately activated this can result in chronic inflammation and autoimmune disease. Advances in immunology research have clarified the role the immune system plays in many different disease areas, even those that have not been traditionally thought of as having an immune component. Charles River’s expert immunologists can support your immunology programs with a wide selection of in vivo and in vitro immunology assays, inflammation models and autoimmune models, across numerous therapeutic areas, like vaccine development, infectious disease, and immuno-oncology.

In a truly translational approach to discovery and development, we combine our inflammation models and autoimmune models with relevant biomarkers like flow cytometry and histologic analysis, for a study design tailored to meet the goals of your immunology programs.

Immunology Assays and Inflammation Models: Advance Your Autoimmune Disease-Targeted Therapies

microbiome, immune system and inflammation models in mice

Our experts explain how combining disease-relevant models, in vitro inflammation models, and autoimmune T cell assays creates a clear picture of how your therapy is reprogramming the immune system.

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Challenges in Immunology Research

Global immunosuppressive drugs that treat autoimmune and auto-inflammatory disease (cyclosporin A and rapamycin) might soon be replaced by newer immunomodulatory therapies targeting the cell types and pathways that drive the disease process. The advantage of such therapies is that the rest of the immune response remains intact, with better outcomes for patients.

Inflammation and autoimmune drug discovery programs that focus on a specific disease area require models that recapitulate the human target disease as closely as possible. It is important to choose best efficacy model to elucidate the effect of your therapeutic. For example, if your target is CD4 Th1 T cells, your chosen autoimmune model should demonstrate a strong Th1 component.

For immunology research programs looking to screen for in vivo target engagement, pharmacodynamic (PD) models may provide an alternative way to demonstrate that your therapeutic is on target before moving to more complex and lengthy efficacy models. Alongside in vivo clinical scores and efficacy, ex vivo analysis of immune cell subsets provides critical information on whether your therapeutic influenced cell behavior (e.g., proliferation, differentiation) in the anticipated manner.

As we see an increasing number of antibody-based therapies heading through the drug development pipeline, it is important not only to consider cross-reactivity onto mouse or proving efficacy in a mouse equivalent of your therapeutic, but also to test using the relevant human immune cell populations.

Our team has developed numerous pharmacology, efficacy and mechanistical actions (MOA) immunology assay and models to support your drug development.

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Understanding MOA Drives Model Selection

Charles River’s immunology platform combines autoimmune models, autoinflammatory pharmacodynamic (PD) and efficacy models with expertise in ex vivo analysis of immune cell subsets and primary human immune cell assays. In addition to guiding your model selection, our team can help you determine if you are engaging your target with the expected outcomes by evaluating the right ex vivo readouts and running relevant assays with human immune cell subsets.

In Vivo Pharmacology PD Models to Further Refine the Compound Selection and Develop Suitable Readouts

  Fluid Based Biomarkers during immunology research

Pharmacodynamics models can drive your immunology assay, before entering lengthy and expensive disease-specific models. Examine the role of a therapeutic outside of the disease setting, to determine if it is hitting its target and modulating the desired cell type.

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Inflammation Model By Therapeutic Area

Immunology assays have become an important tool during a lot of different types of drug development, even for therapeutic areas not known to have an immune component. Charles River has developed extensive experience with those in vitro and in vivo immunology models and are able to advise on the best assays to collect human translational data based on the characteristics of your drug.

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Frequently Asked Questions (FAQs) about Immunology Assays & Autoimmune Models

  • Why target the immune system during drug development?

    When conducting immunology research, it is critical to understand how the complex immune system affects the progression and treatment of disease.

  • How should I choose my autoinflammatory/autoimmune model?

    The model you select should be dictated by the proposed mode of action of your therapeutic and immune cell type you are looking to target. IBD models, for example, are chemically induced models (e.g., DSS colitis) strongly driven by the innate immune system. Therefore, it would not be useful if your therapy was aimed at T cell regulation, in which case the adoptive transfer model of colitis would be more informative. In addition, if your therapy is aimed at driving epithelial repair, it will be necessary to choose a model that is able to resolve. In this case, the DSS colitis model may be a good choice, as upon withdrawal of DSS the epithelial barrier begins to repair, and several cycles of damage can be induced by reintroduction of DSS into the drinking water.

  • Are you able to support ex vivo readouts from your autoimmune models?

    Yes, our immunology research team can support ex vivo readouts of immune cell profiling and function from a variety of tissues. This includes up to 18-color flow cytometry, analysis of cytokines, T cell proliferation in response of re-stimulation with the relevant peptide, immune cell functional assays. In addition, we provide histological analysis.

  • How can in vitro human primary immune cell assays support my immunology research?

    In vivo efficacy models demonstrate that you can inhibit disease progression and severity. However, the human immune system does differ from that of the mouse. Using primary human immune cell in vitro assays gives you data that allows you to translate the mode of action of your therapy into man. Assays can be simplistic in setup such as polyclonal T cell assays through to more sophisticated multicellular routine or custom-built assay systems.

  • Why use pharmacodynamic (PD) models?

    PD models are often an informative and quick way of screening your therapy to determine if it is on target in vivo. Often driven by a specific cell type, these assays can help narrow down lead candidate choices during your immunology research before moving to more lengthy, complex and costly efficacy models.

  • How can you help progress my microbiome therapy?

    Our team of immunologists and microbiologists work together in a multidisciplinary approach to supporting your microbiome therapy development. Our experience across autoimmune, inflammation, tumor and infection models both in vivo, ex vivo and in vitro allows us to support your immunology research program across multiple stages and readouts.