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Nanosphere Releases Preliminary Data from Ultra-Sensitive Protein Biomarker Study

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By Molika Ashford

Early data from an ongoing Nanosphere research program on ultra-sensitive nanoparticle-based assays has demonstrated the technology's ability to detect a collection of promising biomarkers for a number of cancers including bladder, kidney, and prostate.

The company released the early-stage data on the assays' detection achievements in an abstract for the annual meeting of the American Society of Clinical Oncology, to be held June 3-7 in Chicago.

The data shows "that we can do a number of high-sensitivity assays and we can do them in a high-throughput way," Winton Gibbons, Nanosphere's senior vice president of business development, told BioArray News.

In the abstract, Nanosphere researchers described their goal — to develop ultra-sensitive assays for both the discovery of new protein cancer markers that require high sensitivity, and the "evaluation of diagnostic applications." Three of these protein assays — for bladder, kidney, and prostate cancer — have shown clinical relevance in pilot studies, the company said. The firm noted in the abstract that it had examined clinical applications for some of the markers by testing 288 serum samples of bladder cancer, 144 kidney cancer samples, and more than 500 PSA serum samples.

The authors write that "high sensitivity (e.g., PSA LOD

In preliminary data released last year, Nanosphere researchers reported that pilot experiments showed high analytical sensitivity in assays for oxidoreductase, uteroglobin, and PSA. Preliminary results showed 27 percent sensitivity at 100 percent specificity for oxidoreductase in identifying kidney cancer and 41 percent sensitivity with 100 percent specificity for uteroglobin assays ruling out kidney cancer.

For bladder cancer, an oxidoreductase assay showed 18 percent sensitivity at 100 percent specificity in these early tests. Gibbons said these pilot results are being followed up with validation studies for which the company is currently collecting samples.

In addition to the kidney, prostate and bladder assays mentioned in the abstract, Gibbons said, the firm has also been working on colon cancer samples, a "handful" of ovarian cancer samples, and non-cancer kidney diseases.

He said three main areas of importance underlie Nanosphere's work to create these high-sensitivity assays. First, the company hopes to be able to detect proteins that are of low abundance in blood. Second, it believes that a highly sensitive assay allows for possible diagnostics based on other fluids, like urine, where makers are less concentrated. Lastly, higher sensitivity means that markers could be detected even after using sample-preparation methods that Gibbons said lower the concentrations of high-abundance proteins by 100 fold or more.

"The other piece, which we think is just as important, is the high-throughput piece — that we've basically taken our nanotechnology and put it on a robotic system so we can do hundreds or thousands of samples," Gibbons added.

The research has relied on Nanosphere's Verisens high-throughput assay platform, the researchers reported.

Like the Verigene platform behind Nanosphere's work in DNA detection, Verisens is a "multi-step deterministic robotic process," the authors wrote — but aligned for proteins rather than DNA, using "non-isotropically oriented antibodies on functionalized glass" as microarrays to capture protein markers. Gold probes that are 130 angstroms in diameter bind the markers, and the marker-bound complex is quantified through silver enhancement of the functionalized gold, according to the abstract.

In the abstract, Nanosphere's researchers describe the detection of several tumor makers by the assays, including NQO1, uteroglobin, CLC-5, uroplakin, RSOR, p53, CA125, AFP, HE4, CA15-3, CA19-9, beta-hCG, CEA, and PSA.

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Several of the markers, such as PSA and CA125, are already known in relatively high abundance, said Gibbons. Others, like uteroglobin and uroplakin, are "known to exist in general, but in low concentrations, and are currently not measurable in blood, at least not in large amounts," he said.

Additional aspects of Nanosphere's larger research program on high-sensitivity protein assays were presented at the Association for Clinical Chemistry's Oak Ridge conference this April, and in October 2010 at ASCO's Annual Meeting on Molecular Markers in Cancer.

"Our approach to biomarkers is to help physicians get clinically actionable information," Gibbons said. "The kind of marker we'd rather have is one that has a definite diagnosis even if the sensitivity isn't great," he said." What we want to say is, 'Look, if you set the cutoff here, everything above that value has cancer… You may still be left with a number of indeterminates, but the ones you know have cancer, we're hoping to be able to say, 'You have it.'"

The researchers cautioned in each of their presentations that data so far reflects only limited sample sizes and retrospective studies. Nevertheless, they claim that the Verisens platform "is capable of generating more sensitive assays than are currently available for PSA, oxidoreductase, and uteroglobin."

"Bluntly speaking, [Nanosphere is] only now looking for some of the markers and some of the cancers, at the level of finding another set of retrospective samples," Gibbons said.

"We've generated the hypothesis and we're now validating in retrospective samples and that will take a while, so we're not looking at doing prospective studies for a while," he said. "It's more expensive, so we want to be pretty sure we know the answer before we do them."

The key finding of the abstract the company just released, he said is that "across the number of markers — both low abundance and common that we can dilute with sample prep — we can create these high-sensitivity assays and we can run them [robotically] so we can do lots of samples."


Have topics you'd like to see covered in Bioarray News? Contact the editor at mashford [at] genomeweb [.] com.

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