Zebrafish platforms are helping us to study metastatic disease, and a novel tool is helping improve data quality from cancer-fighting immune cells
Tiny vertebrates are Becoming a beneficial player in discovery oncology
Most of the platforms in drug discovery are either in vitro assays based on cells or part of cells or in vivo assays based on vertebrates. Both set-ups come with pros and cons. The zebrafish platform seems to have the potential to combine the advantages of both sides. Zebrafish are vertebrates providing all aspects of an organism like breathing, blood circulation and interaction of different organ systems. On the other hand, they are so small, especially as larvae, that they are easy to scale up. It is even possible to perform zebrafish experiments in a 96-well format. The rate of acquisition of data is also correspondingly fast. In addition, there are strong ethical arguments for conducting more research at embryonic stages in lower vertebrates, in the spirit of the 3Rs. In the upcoming months the predictive and robustness of the zebrafish platform as a part of the drug development process will elucidate the value of this emerging technology. Specifically for oncology, zebrafish platforms have the potential to drive major breakthroughs as the zebrafish mimic the process of invasion and metastasis in a realistic and robust manner
—Julia Schüler, DVM, PhD, Research Director, Discovery Oncology Charles River
A novel way of recovering more viable immune cells from the tumor microenvironment
In animal models the tumor microenvironment is commonly sampled to assess leukocyte infiltration along with cytokine expression patterns. Pharmacodynamic readouts such as these help draw meaningful conclusions on exploratory immunotherapies. When flow cytometry is used for this reason, it generates information-rich data, and when considered for early decision-making in drug pipelines, it is essential that the same data are reproducible. However, their quality can be diminished by inconsistency in sample preparation. Therefore, maintaining suspension cell quality for flow cytometric analyses proves an important pre-analytical factor. Laminar WashTM technology has been offered as a commercial solution to standardize single cell processing in smaller sample volumes. This novel platform reduces experimental variability by eliminating manual washing. Likewise repeated cell pelleting by centrifugation becomes obsolete. Both streamlines an antibody staining protocol for immunophenotyping. This approach continues to be explored for known assay formats based on flow cytometry. By retaining immune cells and removing debris in suspensions prepared from solid tumor resections more viable leukocytes can be recovered for subpopulation analysis. This way of sample handling offers better assessing of tumor-infiltrating leukocyte patterns as part of the datasets evaluating the response to potential cancer immunotherapies. Ultimately, utilizing Laminar WashTM platforms have the potential to set a new standard for flow cytometry sample preparation protocols.
—Christoph Eberle, PhD, MICR Principal Scientist, Oncology, Charles River