NEW YORK (GenomeWeb) — Biocept and Rosetta Genomics said this week that they will pair Biocept's circulating tumor cell isolation technology with Rosetta's microRNA analysis platforms to investigate the possibility of developing blood-based cancer diagnostics and therapeutic response assays.
For Rosetta, the partnership could provide it with additional new product opportunities as it seeks to diversify its current portfolio, which comprises microRNA-based cancer diagnostics that use tissue samples, President and CEO Ken Berlin told PCR Insider. In addition, the foray into CTC analysis could help it land more pharmaceutical development partners seeking to develop liquid biopsy approaches to companion diagnostics.
Meantime, for Biocept, partnering with Rosetta gives it a foothold in the area of microRNA analysis, which fits into the company's strategy of applying its technologies to cellular and cell-free cancer biomarker detection, Biocept CEO Michael Nall told PCR Insider.
Under the partnership, researchers from the companies will explore the use of Biocept's microfluidic channel technology, called OncoCEE, to capture circulating tumor cells from blood samples. The OncoCEE platform works by capturing CTCs in transparent microfluidic chambers approximately 50 microns deep and containing roughly 9,000 posts in a volume of about 24 microliters, according to the company's website.
Specific cells can be immobilized, or captured, using reagents embedded in the chambers, then subsequently removed by shear force and concentrated for downstream lysis and analysis using methods such as real-time PCR or the company's proprietary CEE-selector technology.
Biocept currently uses the OncoCEE technology as the basis for its own liquid biopsy assays, including OncoCEE-BR, which uses FISH and immunocytochemical staining to analyze HER-2 amplification from peripheral blood samples of breast cancer patients to aid physicians with prognosis, monitoring, and therapy selection; and OncoCEE-LU, a multi-parameter assay for lung cancer patients that company executives hope to launch by the end of this year.
However, to date "we're focused mostly on the DNA side … and that's true for both the intact cells and cell-free platforms," Nall said. "We do want to find ways to [assay] all parts of the cells, and we thought that, as a leader in this space, Rosetta makes an ideal partner for us to start to explore the RNA side."
An early pioneer in the area of microRNA analysis, Rehovot, Israel-based Rosetta currently offers four microRNA-based assays — cancer origin, lung cancer, kidney cancer, and mesothelioma — out of its CAP-accredited, CLIA-certified laboratory in Philadelphia.
According to Berlin, the cancer origin and kidney cancer tests rely on microarray technology manufactured for the company by Agilent Technologies; while the lung cancer and mesothelioma assays rely on a proprietary RT-qPCR platform for microRNA analysis. In an email to PCR Insider, Rosetta CSO Dganit Bar said that this platform is TaqMan-based and involves a single reverse transcription reaction.
"It is appropriate for minute RNA amounts and can be used for the quantification of microRNAs as well as mRNAs," Bar said. In addition, the method is extremely sensitive, capable of detecting, for instance, the liver-specific miR-122 when as little as .01 percent of liver RNA is spiked into brain RNA; as well as highly specific, with greater than 100-fold specificity for a single nucleotide mismatch demonstrated for let-7 family members.
As part of the collaboration announced this week, researchers from the companies will use various Rosetta analysis technologies, including the RT-qPCR platform, on the CTCs isolated with Biocept's technology to test for microRNA markers currently offered by Rosetta and to pursue potential new markers.
The partners will conduct a joint proof-of-concept study that will initially seek to determine whether CTCs from lung cancers provide microRNA signatures similar to those previously demonstrated by Rosetta and currently offered by Rosetta in its tissue-based laboratory-developed tests.
"We know this tissue isn't always easy to get, and difficult to get on a repeat basis, so being able to do microRNA profiling in CTCs creates a whole bunch of new opportunities for us," Rosetta's Berlin said. "We've launched four assays … and if we can use some of them with CTCs, it might just create more opportunities for us either as new or next-generation products."
Furthermore, "we know pharma companies in the oncology space are really attuned to this liquid biopsy approach," Berlin said. "We know if we can do microRNA profiling on CTCs and predict response to treatment or monitor patients as they're on treatments … that opens up new opportunities for us, as well, in terms of pharma collaborations."
"We're trying to monetize our … microRNA [analysis] platform through our current products, new products, and collaborations, and this type of effort with Biocept fits in with our strategy," he summarized.
Of the OncoCEE technology, Berlin said that Biocept has "generated some interesting data," without elaborating. "We have looked at other things, and we continue to look at other approaches because there are a lot out there … that seem to be gaining traction and the attention of different groups like pharmaceutical companies," he added. "I've known the company for a long time and I know the technology, so there is some familiarity there."
Some recent OncoCEE data stems from a collaboration between Biocept and the University of Texas MD Anderson Cancer Center to investigate biomarkers in CTCs and cell-free circulating DNA in ovarian cancer. This collaboration was just expanded earlier this month following findings from a study published in July in Cancer Cell in which MD Anderson researchers successfully used OncoCEE in a mouse model of ovarian cancer.
Biocept itself has done some work in the area of RNA. In an email to PCR Insider, CSO Lyle Arnold noted that the company has demonstrated that versions of its blood collection tube can be used to stabilize mRNA adequately to permit in situ mRNA analysis within cancer cells captured using OncoCEE. In addition, company researchers have used its PCR-based CEE-selector assay to detect extremely rare mutations in mRNA, as well as in DNA targets.
However, prior to the Rosetta partnership, Biocept had yet to tap into a microRNA opportunity.
"This shows that there is a different aspect to our business that we're going to start to commercialize and take best advantage of the IP that we have here in different ways," Nall said. "We're always looking for partners such as Rosetta that have offerings that don't compete with what we're trying to do internally, yet still take advantage of [our] expertise. And of course the most important thing is this is going to make it better for patients, as we move these tissue biopsies to blood-based tests, and it costs less money, and is more indicative of what's going on in that patient in real time."