With the addition of an Immunotoxicologist to our laboratory, MSU In Vivo is positioned to offer a variety of services in Immnotoxicology and Immunopharmacology.
The In Vivo Facility at Michigan State University offers both custom in vivo model and custom immunoassay development to assess immunopharmacology relevant to your drug candidate and target. These capabilities include development and analysis of target-specific immunophenotyping panels, cytokines/chemokines/inflammatory mediators, ex vivo innate immune function (ie, phagocytosis, respiratory burst, NK killing assays, etc.), and ex vivo adaptive immune function (ie, T-dependent antibody response [TDAR] assays, proliferation assays, antigen-specific activation assessments, etc.). Through the use of state-of-the-art flow cytometry, in vivo imaging, multiplex ELISA, qPCR, and microscopy technologies, we are capable of developing a wide range of custom models that assess immunopharmacology of both small molecules and biologics. The In Vivo Facility is also experienced with infectious disease, tumor, and autoimmune preclinical models. We collaborate with investigators to develop and implement proof of concept studies in disease models in order to demonstrate efficacy of therapeutics.
Pharmacodynamic Biomarker Development
The In Vivo Facility collaborates with investigators to develop custom translational target-specific pharmacodynamic (PD) biomarker assays in rodent and non-rodent species that can be utilized throughout the drug development process. It is often critical to integrate pharmacodynamic assessment of immunotherapies into preclinical toxicity studies to substantiate the safety assessment and aid in human dose determination. This has been particularly true with the recent wave of immuno-oncology biologics (ie, anti-CTLA4, anti-PD-1, anti-LAG-3, etc.), as these therapeutics have demonstrated limited toxicity in preclinical models, rendering pharmacodynamic biomarkers essential in the interpretation of safety study data. We aid in the development of robust and clear-cut pharmacodynamic biomarker assays targeted early in the drug development process that can be translated across species with the potential to be implemented in clinical trials.
In addition to immunopharmacology model development, the In Vivo Facility collaborates with investigators to evaluate potential immunotoxicity of drug candidates, as many immunoassays can be applied to both immunotoxicology and immunopharmacology assessments. While evaluation of immunotoxicity is not recommended for all therapeutics early in the drug development process, it may be critical under circumstances where 1) the drug directly targets a component of the immune system, 2) the drug maintains structural similarity to an immunosuppressive compound, 3) previous in vitro studies suggest an effect on the immune system, or 4) the drug is intended for use in an immunocompromised population of patients. Understanding potential for immunotoxicity early in the development of a drug can identify off-target effects on the immune system or exaggerated pharmacology, which can drive important decisions regarding a lead compound and increase confidence in the successful development of a therapeutic. We work with investigators to develop non-GLP immunotoxicology studies for both biologics and small molecules using a case-by-case approach.
Investigative Immunotoxicology Model Development
The In Vivo Facility is uniquely positioned to draw upon the collective expertise of a diverse pool of faculty at Michigan State University in the fields of Immunology, Microbiology, Pharmacology, and Toxicology to drive the development of in vivo models that determine mechanisms of immunotoxicity. The occurrence of an adverse event during preclinical or clinical studies with an immunotherapeutic often precipitates the need for understanding the nature of the toxicity. Investigative in vivo studies, frequently involving transgenic or knockout models, are utilized to recapitulate these findings with the goal of determining the mechanism of toxicity.