prediction of Efficacy and Drug-induced toxicity is critical to prevent
liabilities being detected at a late stage when considerable time and expense
has been invested in a project. Following several well publicized drug
withdrawals from the market due to toxicity and inefficacy, the industry is now
keen to adopt approaches which ensure efficacy end points and any potential
adverse effects are detected at an early stage. However, developing assays
which can accurately predict human toxicity can be challenging, especially in
the case of distinctive toxicity which only manifests itself in a small
percentage of the population.
Human cell-based models tend to be the most popular for assessing drug-induced toxicity in vitro. These assays have several advantages including being of human origin and allowing specific mechanisms of toxicity to be explored. Through the 3D cell models, coupled with sophisticated imaging technology, more complex models can be developed and analyzed. The longevity of these models allows for repeat dose regimens to be tested, and the models more closely represent the cell-cell interactions observed in vivo.
Moreover, establishing 3D organotypic models isn’t always straightforward. The research involves investigating a huge array of variables to assess the optimal conditions in terms of time points, cell types, seeding densities and co-culture cell ratios as well as the most appropriate endpoints and analytical techniques.
Cellomatics Biosciences have spent considerable time and effort establishing robust in vitro 3D models for predicting efficacy and safety of new chemical entities.
Keywords: Spheroid, cancer, tumour, immune oncology, pre-clinical drug discovery, DNA damage, breast cancer, metastatic, chemotherapy, PARP inhibitor, Talazoparib, bleomycin, MDA-MB436, cell imaging
Fig.1/ Fig.2: https://cellomaticsbio.com/images/3d-organ-day-2-6.png
Cellomatics Biosciences developed and validated several 3D and Spheroid Organ Specific Models as follows: Lung NCI-H446, A549 and Calu-1; Breast BT474 and MDA-MB436; Ovarian SKOV3 and OVCAR3; Prostate DU145; Pancreatic CaPan1; Colorectal HCT116; Endometrial AN3CA; Glioblastoma U87MG; Stomach HGC-27. These models, which are formed from primary cells or derived cells, better mimic the in vivo cellular environment and often have improved predictivity when compared to the 2D monolayer equivalents