NEW YORK(GenomeWeb) – Proteomics firm Caprion is collaborating with diagnostics company Abcodia and Cancer ResearchUK on discovery and validation of serum-based protein biomarkers for colorectal, lung, esophageal, and pancreatic cancers.
In the first stage of the project, Caprion will use its discovery and targeted mass spec platforms to analyze roughly 400 samples from the UK Collaborative Trial for Ovarian Cancer Screening (UKCTOCS) collection, a biobank consisting of more than 5 million serum samples taken from 200,000 initially healthy volunteers, some 27,000 of which have subsequently been diagnosed with various cancers.
Abcodia announced in December that it had selected Caprion, along with Asuragen and the Austrian Institute of Technology, as partners in its biomarker work using the UKCTOCS samples, to which Abcodia has an exclusive commercial license. Asuragen will be looking into microRNA-based markers, while the AIT will investigate cancer-related auto-antibodies.
According to Caprion CSO Daniel Chelsky, the company was one of several proteomics outfits considered for the collaboration.
"We went through a first round [with Abcodia] that was really designed to assess our capabilities," he said, noting that among the project's requirements are platforms capable of analyzing large numbers of analytes with high reproducibility across many samples.
Caprion has considerable experience in developing protein biomarkers for clinical use as the company did a significant portion of the biomarker discovery and validation work for Integrated Diagnostics' Xpresys lung cancer test, which, upon its launch last year, became the first multiplexed proteomic test to go to market using MRM-MS on a triple quadrupole instrument.
Indeed, Chelsky said, Caprion's work with Indi was key to developing its clinical proteomics capabilities.
"Diagnostics is a very special place where the requirements go beyond simply identifying differentially expressed proteins," he said. "Coming up with classifiers of disease is really a step beyond, and working with Indi made a big difference for us in our capabilities."
For discovery, the company uses a label-free shotgun-style mass spec assay on a Thermo Fisher Scientific Q Exactive instrument. While data-independent acquisition mass spec methods like Swath are growing in popularity due, in part, to what some researchers consider their more reproducible quantitative data, Chelsky told GenomeWeb that Caprion believes its shotgun mass spec platform remains a better option for clinical biomarker development.
"Swath is a very interesting approach that we are looking at very closely," he said. However, he added that he thought DIA mass spec was still "at the research stage at this point. We don't believe that it's ready for prime-time for a company like ours that really has to operate with a very well characterized platform."
Chelsky said that DIA approaches could in a few years prove "an excellent approach" for the company's biomarker discovery efforts, but that more software development and wider availability was needed.
Using its discovery platform, Caprion can reproducibly quantify in the range of 1,500 proteins in serum, Chelsky said. The plan, he said, is to identify candidate markers in this first stage of the collaboration and then move those candidates along with other proteins identified through methods like literature searches to a targeted validation phase.
For this, Caprion uses multiple-reaction monitoring mass spec on triple quadrupole instruments – either AB Sciex's 6500 or Agilent's 6495. Initial assay development is easier on the AB Sciex 6500, but the Agilent 6495 offers higher sensitivity and can handle higher sample volume, which further improves sensitivity, Chelsky said, noting that "for diagnostics the instrument of choice among our collaborators seems to be the Agilent instrument."
The company has also begun using high-resolution instruments – the Q Exactive, specifically – for targeted quantitation experiments, particularly when looking at a small number of proteins, Chelsky said, adding that "it is certainly a very simple and easy way to do a targeted project."
For larger targeted assays looking at hundreds of proteins, however, MRM on a triple quad remains the best option, he said. "The Q Exactive isn't really built for that, so it's really best to go to the triple quad for these large-scale studies."
While Caprion will likely be looking at around several hundred proteins in the targeted phase of the Abcodia project, the company has recently developed MRM assays capable of quantifying as many as 1,500 proteins per experiment and plans to launch a 1,500-protein MRM assay in human plasma this summer, Chelsky said.
Caprion entered the biomarker discovery panel space earlier this year with the May launch of its CNS ProteoCarta panel, an MRM-based, 142-protein panel for the study of central nervous system diseases. The 1,500-protein assay will be among the largest commercially available biomarker discovery panels – significantly larger than Myriad RBM's 300-assay Human DiscoveryMAP product and comparable to the expanded, roughly 1,500-protein SOMAscan assay that Somalogic is planning for 2015. (The current SOMAscan assay measures 1,129 proteins.)
The 1,500-protein panel will consist of markers of interest to researchers studying areas including oncology, cardiovascular disease, and inflammation as well as all protein biomarkers currently in clinical use, Chelsky said.
In terms of the Abcodia work, Caprion will look first at colorectal cancer and expects to take around five months for the initial discovery study and around four months for the targeted analysis.
Chelsky said that while it remains to be determined exactly how far into clinical validation Caprion will carry any markers emerging from the project, "the expectation is that we will carry this quite far, and we are certainly interested in a diagnostic assay for the clinic."
Abcodia and CRUK will hold rights to any such diagnostic, but Caprion would be potentially interested in establishing commercial versions of the test in markets outside theUK, he said.
As Caprion CEO Martin LeBlanc told GenomeWeb in a 2013 interview, the company is working to establish a CLIA lab with the aim of offering not only its own diagnostic products but also those of outside companies looking for a Canadian partner.
"Obviously, though, this is very early in the process, and it takes years to get to that point," Chelsky said regarding the Abcodia collaboration.