Animal models play a crucial role in drug discovery and development. While in vivo animal models are preferred for use in drug discovery efficacy testing at the target validation and late lead optimization stages, in vitro models have gained popularity for candidate selection from hit to lead and within lead optimization. Therefore, the cell models used for this purpose are subject to constant improvement through the implementation of innovations in the areas of analysis, automation, and cell culture conditions.
Bringing a safe and effective drug is extremely time consuming and costs between $2-3 billion. The main reason for the enormous cost is the high failure rate of 90% for all investigational new drug (IND) candidates in clinical trials, due to lack of efficacy and safety due to poor translation of results from the applied in vivo and in vitro methods to humans and especially to patients. In particular, safety testing of new chemical entities in healthy animals and their translation to sick patients could explain this issue. Disease may understandably make patients more susceptible and thus narrow the underlying therapeutic window compared to healthy subjects. There is an increasing need to improve the current testing paradigm, particularly when considering the ongoing trend in pharmaceutical industry to move from small molecules to new therapeutic modalities, such as biologics, oligonucleotides, peptides or bispecific human antibodies, gene and cell therapy, which have been demonstrated not to work in animal models. The main reason for this is that the immune system of rodents is fundamentally different than that of humans. These differences mean that is not possible to predict pharmacological and toxicological responses in animals for human biological therapeutics. The lack of innate and adaptive immunity, mediated by resident and circulating immune cells in most traditional test models might also be a reason for not correctly reflecting the disease state as it occurs in patients.
Over the last decade micro-physiological systems (MPS) have been demonstrated significantly superior properties for predicting drug safety and efficacy compared to classical 2D cell culture systems. One of the important advantages of the these physiologically relevant MPS is the incorporation of multiple cell populations including the immune cells allowing for innate- and adaptive-immune responses following compound testing and negating interspecies differences between pre-clinical animal models and man. Finally, these systems allow for the replacement, reduction and refinement of animal testing.
In this special issue, we invite original research and reviews focusing on physiological and pathophysiological industrial compatible in vitro MPS designed for next generation testing preferably under immune competent conditions on the plates. Model systems should be characterized and validated for the industrial setting demonstrating technical feasibility (throughput), economical and ethical value. The resulting data should have better translatability to diverse populations as well as to individual patients through using cells or tissues from donors with respective genetic background or underlying disease. The corresponding system should have high quality (reproducibility, robustness), reasonable throughput for big data generation (scalability). The systems should be advanced and further developed for the routine industrial applications beyond proof of concept and thus have high impact for decisions made during the pharma drug development process.
We accept different article types including Mini-Reviews, Brief Research Reports and Perspectives. A full list of accepted article types, including descriptions, can be found at this
link. Comprehensive studies are highly encouraged.
Topic Editor Dr. Armin Wolf is Chief Scientific Officer and Dr. Wolfgang Moritz is Head of External Collaborations and IP at InSphero AG. The other Topic Editors declare no competing interests with regard to the Research Topic subject.