The development of CTC-derived models specific to PDAC has remained challenging due to the limited number of CTCs retrieved from patients’ samples.  

In work led by our collaborators, we demonstrated that our proprietary recombinant VAR2CSA, which specifically binds oncofetal chondroitin sulfate, retrieved more live CTCs than single antibodies for traditional CTC biomarkers (EpCAM, CD7, or FAP). Further, VAR2CSA retrieved an identically high number of CTCs while retrieving significantly less white blood cells than the combination of the same three antibodies.

VAR2CSA retrieved a consistently high number of CTCs from localized (early stage) to advanced (late stage) PDAC patient samples. Interestingly, retrieval of CTCs with VAR2CSA enabled differentiation between benign and malignant intraductal papillary mucinous neoplasm – a precancerous condition.

Using this retrieval and isolation strategy, our collaborators generated CTC-derived PDAC in vivo models that were functionally heterogeneous and with more invasive and metastatic potential, and therefore more closely reassembling human conditions. Interestingly, in vitro CTC-derived cultures could be employed for drug screening, accurately reflecting patient response to treatments.

This study highlights the importance of CTC-derived models in advancing PDAC treatment, and the potential of VAR2CSA and oncofetal CS in retrieval of CTCs in pancreatic cancer. Further, it shows the potential of targeting oncofetal chondroitin sulfate for the development of cancer therapeutics and diagnostics.

Read more about it here: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00413-0