NEW YORK (GenomeWeb) – Diagnostics startup IvyGene plans to launch a blood-based cancer detection test next month that relies on an epigenetic approach initially developed by researchers at the University of California San Diego.
A holding of a company called the Laboratory for Advanced Medicine, which has previously worked mainly with proteomic tests, IvyGene is launching the test this month through its CLIA lab, General Manager Nick Miner said in an interview.
Members of the UCSD group who developed the core methodology published a new study on the method last week in Nature Materials, in which they worked with a handful of Chinese institutions to develop a classifier that could distinguish patients with liver cancer from healthy controls, and to quantify disease stage or progression.
Analyzing 1,098 hepatocellular carcinoma patients and 835 normal controls, the authors were able to develop and measure ctDNA methylation patterns that were “highly correlated with tumor burden, treatment response, and stage.”
The technique follows on a methodology described in Nature Genetics earlier this year by UCSD bioengineering professor Kun Zhang and colleagues that relies on the detection of unique patterns of co-methylation across numerous CPG sites in circulating cell-free DNA.
Although this most recent demonstration of the approach was limited to liver cancer, researchers wrote that they believe that it should be applicable to the detection of a variety of cancers.
In another paper published this past July in the Proceedings of the National Academy of Sciences, the same team of researchers reported on their identification of cancer markers in a training cohort of 1,619 tumor tissue samples and 173 matched adjacent normal tissue samples.
Using whole-genome bisulfite sequencing and machine-learning methods, the team was able to distinguish cancer tissue from normal tissue with more than 95 percent accuracy. The researchers also picked out a majority of CRC metastases that were specific to either the liver or the lung.
IvyGene's Miner said that the firm's commercial offering, already advertised on the IvyGene website, is a pan-cancer assay. Unlike the method described by Zhang and colleagues, which involves broad bisulfite sequencing, IvyGene has adapted the approach to digital PCR using BioRad's droplet digital platform.
As an LDT, the assay is outside the current purview of the US Food and Drug Administration, and is described as a confirmatory diagnostic, which yields a readout on the presence or absence of cancer, as well as quantification that can indicate progression, or potentially response or non-response to therapy.
On the firm's website, customers are advised that the assay is not approved for screening in asymptomatic patients with no other positive or suspicious diagnostic results. The test is targeted mainly at clinicians who suspect cancer in a patient due to some sort of risk indicator like a mammogram or PET scan result, high PSA, or genetic risk mutations like BRCA1/2.
However, Miner said that the firm believes it can also be useful for monitoring patients in remission for the reemergence of cancer. And, because the test allows for a quantitation of methylated versus unmethylated DNA, it could also help determine if a particular treatment is working by detecting changes in the amount of methylated DNA molecules.
The company has not yet published data that describes the validation of its ddPCR-based adaptation, though it states on its website that sensitivity and specificity are predicted to be at least 85 percent for detection of stage I-IV cancer.
In addition, IvyGene's Lab Director David Taggart said in an interview that although simplifying the analysis to 10 or 20 CPG sites (rather than the 1,000 or 2,000 that can be analyzed with targeted methylation sequencing) doesn't significantly affect sensitivity.
IvyGene is not alone in turning to methylation and epigenetics in the blood-based cancer detection space. A number of other groups have recently published similar findings, including one team from the Hebrew University-Hadassah Medical School, and another from Jay Shendure's lab at the University of Washington, which launched a new company called Bellwether Bio, to commercialize a method for inferring the origin of circulating cell-free DNA based on patterns of nucleosome spacing.
Others have already launched tests with a similar indication as IvyGene's using circulating DNA mutations, or circulating tumor cells rather than methylation patterns.
But while research has advanced significantly over the last several years, there is still a lack of clinical utility data that persuasively proves that blood-based tests, whether mutation-based or methylation-based, are appropriate for early detection.
Yuval Dor, who led the team from Hebrew University that also published on the use of co-methylation signatures for detecting cancer, said in an email that without published data that speaks specifically to the pan-cancer ddPCR method in question, there is no way to be sure at this point that the test IvyGene is commercializing is sound.
To support clinical use, it is also important to make sure that there is evidence specifically showing the sensitivity of a method in detecting early-stage cancers, he added, so that will be something important to look for in future publications.