Disease Models

Many drug candidates fail in clinical trials due to insufficient efficacy, toxicity, or pharmacokinetic shortcomings. Therefore, predictive preclinical in vitro disease models for evaluating disease hypotheses and for the differential validation of activity profiles of drug candidates are necessary. The ITMP sites have long-standing experience in developing human in vitro “disease models” that can be used to characterize drug candidates with regard to their pharmacodynamics and pharmacokinetics. In addition, new therapeutic targets can be identified and validated. The effectiveness, bioavailability, and off-target effects of drug candidates are assessed to identify lead candidates early and to exclude potentially unsuitable candidates. The range of human-experimental in vitro models forms the bridge from basic research to the clinic and can be effectively complemented by stem cell and organoid models.

Core Expertise:

• Primary cells & iPSCs: using immune cells (e.g., T-, B-, NK cells, neutrophils), fibroblasts, and keratinocytes, as well as iPSC-derived models from healthy donors and patients
• Specialized cell lines: employing established human mast cell lines (e.g., LAD2), liver cell lines (e.g., stellate cells, LSECs) and mesenchymal cells (e.g., chondrocytes, synovial fibroblasts) for targeted investigations
• Modern analytics & genetics: use of multiparameter immunophenotyping, single-cell sequencing, and CRISPR/Cas9 modifications
• Complex in vitro systems: conducting co-culture models (e.g., hepatocytes/immune/intestinal cells), bioavailability testing, off-target effect assays, and specific degranulation assays for functional testing
• Ex vivo & provocation models: investigation and testing of compounds in human skin models (microdialysis, microneedle-based interstitial fluid collection) and provocation tests such as urticaria and allergy models

Objectives/Services:

• Target validation and efficacy testing of substances
• Characterization of off-target effects of substances
• Bioavailability testing / in vitro pharmacokinetic studies