Engineered proteins possess a great therapeutic potential, but their development as novel therapeutics is impeded by the lack of in vitro models that accurately mimic human physiology. Furthermore, it is often challenging to extrapolate results from animal models to the human situation, and there is an increasing societal pressure to investigate alternatives for animal research due to ethical concerns.
In a study conducted by Wouter Verdurmen, assistant professor, and PhD candidate Valentina Palacio-Castañeda from the Department of Biochemistry, in collaboration with researchers from the Institut Curie in Paris, an alternative approach to study therapeutic protein behavior and delivery in complex 3D microenvironments was developed. The research was published on May 18th in the special issue Cancer-on-a-Chip: Applications and Challenges from the journal Cancers.
The study employed a hybrid approach combining mathematical modeling with 3D in vitro models, including tumor spheroids and a tumor-on-a-chip device. Mathematical modeling was utilized to simulate the delivery of engineered therapeutic proteins targeting cancer cells and to predict the biological activity. By cross-comparing simulated and experimental data from 3D models, the researchers were able to correctly predict the best dose needed to deliver therapeutic proteins for eradication of tumor cells, while leaving the surrounding non-tumor cells untouched. This study shows the potential of combining computational approaches with novel in vitro models to advance the development of protein therapeutics. The group of Verdurmen focuses on investigating cytosolic delivery of engineered proteins targeted to specific cell surface receptors and uses different in vitro 3D and organ-on-a-chip platforms and in silico studies that aid in the rational development of a next generation of protein therapeutics.
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