Test replaced LDT, offering better ease of use and more comprehensive targets
At CPO (Cellular Phenomics & Oncology), a Berlin-based company specializing in cellular phenomics and oncology, scientists are making significant progress in precision oncology by combining patient-derived, three-dimensional cell culture models with Luminex-based DigiWest® technology. The resulting data from this approach can inform the development of targeted therapies and treatment selection, and delivers real-world clinical benefit.
According to Christian Regenbrecht, CEO of the company, CPO’s PD3D® (patient-derived 3D) cell culture models allow comprehensive drug screening of individual drugs, as well as combination therapies. His team has generated more than 400 of these cell culture models from a wide variety of different tumor entities for pharmaceutical and biotech companies. PD3D models are similar to organoid models, making it possible to recreate the tumor’s native architecture for the best approximation to its in situ form and function. They can be used as tools for preclinical and translational research, such as drug screening in the preclinical context as well as in CRISPR experiments, but increasingly PD3D models are also making their way as avatars for predicting patient response in ongoing clinical trials.
Quicker Results with DigiWest
The CPO team was eager to include proteomic results for its models very early in the developmental process, and adding the DigiWest technology made that happen. The team had previously considered mass spectrometry, but it wasn’t a fit because the results took too long to be useful for clinical work. DigiWest, on the other hand, is a multiplex immunoassay technique that can quantify as many as 800 analytes in a single reaction. This approach allows Regenbrecht and his colleagues to deliver results in 7 to 10 days, complete with information about post-translational protein modifications such as phosphorylation and acetylation.
In addition, DigiWest works well with the precious tissue samples with which CPO typically works. “We have only little amounts of tissues, cells, and therefore protein,” Regenbrecht says, noting that they must generate a great deal of information from each small sample. “DigiWest is of benefit to us because it needs little amounts of input material, and we gather a high-density set of output information.”
Regenbrecht adds that DigiWest “is a robust assay that is highly reproducible, and so the data would also be reliable for clinical utilization. But for the moment, for our customers in the pharmaceutical field, it is very important that we can provide data they can rely on for future experiments.” For example, a recent analysis of samples from a patient with colorectal cancer revealed drug responses that varied by as much as 30-fold, indicating that a combination therapy might be the best treatment course. By using DigiWest on these models, CPO scientists identified the mechanism responsible for aberrant activity in the MAP kinase pathway.
More Work Ahead
Looking ahead, Regenbrecht believes that cell modeling will need to represent even more complexity, such as incorporating immune components or vasculature. He also knows that in these early days of precision oncology, stakeholders like CPO have to carefully balance the promise of what can be done while still being appropriately cautious about a novel approach.
“We are presenting data that was unthinkable two years ago,” he says. “We are at the forefront of medicine.” Still, though, work needs to be done on how to deliver this information in a way that makes the most sense for the physicians, oncologists, and pathologists responsible for dealing with this kind of data at the bedside, he adds.
For more examples of DigiWest in action, check out these publications:
- DigiWest for biomarker discovery
- DigiWest for characterization of compound actions
- DigiWest for deciphering of Wnt signaling
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