The mosaic approach relies on five principles:
human - in vitro – comparison to chemical related drug – high risk population – complex & unique.
- human: DH predictions should be based on human material: DH reactions are mostly not predictable by animal experiments.
- in vitro: it is an in vitro approach – relying on human cells and in vitro solubility of the compound to be tested.
- comparison: the mosaic approach has its roots in research done with cells of patients with DH reactions. The tests are thus based on knowledge gained from other drug hypersensitivity reactions. For some drug classes the cells of affected patients (or their transfected TCR) may be available.
- high risk population: a very unique possibility of the mosaic approach is the use of cells and cell lines derived from patients with multiple drug allergy syndrome. These patients may show a higher readiness to react to a novel drug as well, and the analysis of such cells may provide a more sensitive parameter to detect a DH potential of a new drug.
- complex and unique: DH reactions may evolve due to the hapten/prohapten like feature of the drug. Such features of a drug are often already detected in the pre-clinic or by protein binding studies. But no tests are available to detect the stimulatory potential of a drug based on the p-i concept.
In summary, the mosaic approach offers studies on the innate immunity, as well as an unique platform to test adaptive immunity and the p-i concept. It can also be suitable to evaluate the cross-allergenic potential of a new drug, which is chemically/structurally related to an established drug.