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Vortex CTC Platform Shows Potential for Discovery of New Classes of Cancer Biomarkers

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NEW YORK (GenomeWeb) – Investigators have begun to report on new applications of Vortex Bioscience's circulating tumor cell platform, which it commercialized late last year as the VTX-1. Recent reports have included data on existing biomarkers like EGFR and PD-L1, as well as newer investigations into things like the functioning of cells, which would be impossible without the system's ability to separate and partition viable CTCs.

In a study published last month in Proceedings of the National Academy of Sciences, researchers at UCLA led by Vortex Co-founder Dino DiCarlo used an earlier version of the VTX-1 technology to study not just the molecular profiles of individual CTCs but also their biochemical activity.

The ability to study cancer and identify ways that it can be stalled or caught early is limited by the inability to examine the disease at cellular and molecular levels, in real time, and in situ as it occurs in the body.

But technologies continue to be developed that can provide closer and closer recapitulations, and more and more exacting measurements – such as molecular platforms that provide a parallel readout of both tumor genetics and the molecular signaling that goes on in the tumor microenvironment, liquid biopsy technologies that allow frequent resampling to track changes in circulating DNA over time, and, increasingly, tools that allow the isolation and profiling of circulating cancer cells, either en masse, or individually.

For DiCarlo and colleagues, the goal was to develop a way to be able to look at the function of CTCs "in a situation that is as close as possible to in vivo," DiCarlo said.

The VTX-1 uses a microfluidic chip to capture CTCs in what the company describes as "micro-scale vortices" based on physical properties like how big a cell is, or how easy it is to deform. CTCs are trapped in these microscopic currents and eddies, while red and white blood cells flow past.

"There are a lot of technical challenges to be able to get to these measurements [of cell enzymatic activity]," DiCarlo said. "But with the combination of the Vortex platform, and the approach that my student Manjima Dhar (the study's first author) developed, we can release the cells into droplets very quickly after washing away all the serum around the cell."

If you don’t isolate the cells that way, the background of enzymes is too high to be able to detect the cell's excretion, he added. In a statement, the group disclosed that the Regents of the University of California have filed a patent for the integrated vortex capture and droplet generator device, but Vortex has not disclosed whether it has licensed or plans to commercialize the droplet generation method.

In the study published last month, DiCarlo and colleagues studied samples from a handful of advanced prostate cancer patients and normal controls, looking at whether there were patterns in how cells from the cancer patients exuded a type of enzyme called a matrix metalloprotease, or MMP, which has been linked to the spread of cancer.

"Getting functional cells that are actively secreting was really interesting to us," DiCarlo said. "Even the question of whether these CTCs are alive, or are active, there wasn't a great answer to that before," he added.

Overall, the team analyzed cells from 11 people: seven with late-stage prostate cancer and four who were healthy. Promisingly, in terms of the power of the technology to yield new biomarkers, the researchers saw that MMPs were produced at higher levels in the advanced disease patients. The authors wrote that they were also able to see that MMP levels were correlated with poorer prognosis.

According to DiCarlo, there could be translational value in the findings. "Drug companies have been developing inhibitors targeting [MMPs] based on the fact that invasive tumors stain highly for these [molecules].

However, he said, many clinical trials of these drugs have now failed. "The hypothesis we had is that maybe they are failing because not all of these cancers are being driven by this [marker on a functional level,] so [this kind of] biomarker could maybe improve the success of the trials," he explained.

Recent research has also suggested that MMPs may play a role in immune evasion, and so could also have possible companion diagnostic utility in helping identify patients for new immunotherapy treatments.

Because the fluidic system that Vortex has developed allows analyses of cells in isolation from one another, there could also be opportunities to correlate the activity of individual cells — their live expression of certain enzymes or proteins — with single-cell genomics, something DiCarlo said his group is now hoping to investigate.

Vortex CEO Bob Englert said this week that the company also saw interesting data presented by a user of the system at the Clinical Biomarkers & World CDx summit in Boston last week, that speaks to the ability to interrogate potential new biomarkers.

University of Maryland researcher Stuart Martin, who also has worked with Angle's Parsortix system, applied the VTX-1 to isolating CTCs that have what he calls "microtentacles," which are structures that appear to contribute to cells' ability to seed metastases.

In the meantime, the Vortex platform continues to inform investigations into more established genetic alterations. Earlier in the year, researchers shared data at the annual meeting of the American Association for Cancer Research in which they developed a method to collect plasma, isolate CTCs using the VTX-1, and then search for EGFR mutations in both cell-free DNA and in the isolated tumor cells.

Investigators studied blood samples from 15 non-small cell lung cancer patients and reported that there were cases in which EGFR mutations were only present in the CTCs and not in cfDNA, and vice versa, suggesting added value for the dual approach.

Another poster described experiments looking at PD-L1 expression in isolated CTCs, also in NSCLC.

Vortex has not detailed whether it has commercial interest in supporting clinical translation of EGFR or PD-L1 specifically, but the firm has stated as its goal the provision of technology for the development of diagnostic tests. The company highlighted the application of VTX-1 to these clinical biomarkers in April, and researchers presenting the data earlier this year described their results as illustrating potential for "clinical applications."

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