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PK / PD | Esco VacciXcell

PK / PD

Over the last few decades the safety and efficacy of a drug is evaluated by carrying out the tests on living animals (in vivo tests). More recently research efforts are focussed to find new solutions to replace and reduce animal models for drug testing due to economic, regulatory and ethical reasons. Though Xenograft animal models in cancer are inexpensive way of generating in vivo tumors using the appropriate human and animal cell lines, they suffer from the drawback of their comprised immune system which do not mimic the behavior of naturally occuring cancers in humans. Studies and data show that the average rate of successful translation from rodent models to clinical cancer trials is less than 8% and this is mainly because the stroma-tumor interactions in animal models are not the same as in human models.

Cell cultures have been used for screening drugs (in vitro), but the ways cells behave in a dish is not the same of how they behave in the body and therefore there is a need to create a human tumor microenvironment (for cancer treatment). It is imperative to switch from 2D cell cultures to 3D in order to create cellular models that better captures the complexities of tumor biology. Development of such 3D models would possibly eliminate the differences that are normally observed in rodent models and would enable drug testing directly on human. Production of such 3D models would certainly require a suitable bioreactor and proper cell culture methodology that is robust and scalable. Microcarriers and culture in bioreactors3 can be used for large scale production of cells but is limited by the maximum possible cell density because of limited oxygen supply, physical damage to the cells due to agitation and accumulation of the toxic metabolites.

Our Tide motion bioreactor with unlimited oxygen supply and maximum surface area for high density cell production. Tide motion pertains to the oscillation of culture medium into and out of the matrix vessel that intermittently exposures the cells to aeration and nutrition. The upward oscillation exposes the cells to nutrition, while the downward oscillation exposes the cells to aeration and at the same time washes away products and wastes. This gentle oscillation produces no air bubbles and causes very minimal shear stress leading to production of high-quality cells a prerequisite for 3D models. The Tide motion bioreactor can be adopted as a simple system for high population density cell culture and for large scale production.

Our Bioreactor are therefore suitable for the production of 3D cell culture models with human cells enabling for applications on humans. Moreover these 3D cell culture models also provide better control on conditions and offer a convenient experimental designs in pharmacodynamics and pharmacokinetics. The 3D culture condition can be modified to include factors or proteins quite like a tissue or tumor microenvironment. It is also possible to keep the gene and protein expression levels of cells and hence their cellular behavior similar to an in vivo environment narrowing the gap between in vitro and in vivo drug testing opening up the possibility of a decline in the use of animal models.