Webinar FAQ: PDX Models in Drug Discovery Assays
Patient-derived xenografts (PDX) are the most predictive and translational preclinical xenograft models available for oncology research. Novel platforms are expanding their use into in vitro and ex vivo drug discovery assays, opening new applications for PDX throughout the preclinical drug discovery pipeline.
This post collects the most frequently asked questions from our recent webinar, with answers from Dr. John MacDougall, Global Director, Scientific Engagement.
How long does it take CrownBio to grow and harvest a PDX?
The timeframe to grow and harvest a PDX depends on the model. Slow-growing models can take in excess of ninety days. Most models, on average, require approximately thirty to sixty days.
How sure are you that the PDX models keep heterogeneity over time/passages, and that a clone is not accidentally selected?
That cancers resulting from the engraftment of PDX tissue retain histological morphology is strong support for the maintenance of heterogeneity. With this in mind, CrownBio generally doesn’t exceed ten serial passages of PDX models.
During how many passages in vitro and how many passages in vivo would tumor cells maintain their original morphology and genotype?
This is a difficult question, because the changes that happen can be subtle and occur over time, therefore it is hard to put a solid number on passages. Generally, try to not use PDX models over passage 10.
What is considered in vitro for cells derived from PDX, and what is considered ex vivo? Is the only differentiator the type of assays?
I tend to differentiate between "in vitro" and "ex vivo" based on the source of the cells. If the assay is being run on cells that typically grow in culture, I would refer to that as an "in vitro" study. If on the other hand the cells are taken from an animal and then assayed, I would refer to that as an "ex vivo" study.
Can ex vivo experiments be performed with frozen material? For example, frozen lung tissue ex vivo post-freezing used in a T cell response assay?
If yes, which functions of the tumor cell will most likely be impacted compared to fresh cells?
If the material is cryopreserved, it might be possible. However, I would imagine that there might be an unacceptably low level of viability to perform robust assays.
Are there multiple cell types in 3D TGA models?
If the source of the tissue is in vivo, for an ex vivo assay, then there will be cancer cells present in addition to cells from the tumor microenvironment.
Do you have any comparable information to share for AML or other leukemia PDX models that CrownBio has tested?
Is it possible to create a PDX SJL mast cell KO mouse? We have found a treatment that arrests the progression of MS, ALZ, ALS, and more by switching Th-17 back to Th-2. We need a humanized mast cell KO to determine dosing.
Your treatment sounds very interesting. I'm sure a mast cell KO mouse can be generated, although CrownBio doesn’t perform custom animal engineering directly. This would have to be initiated through a third-party vendor.