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Thermo Fisher, Newman-Lakka Collaborating on Mass Spec Assays for Cancer Biomarkers


Thermo Fisher Scientific said this week that it will collaborate with the Newman-Lakka Institute for Personalized Cancer Care at Floating Hospital for Children at Tufts Medical Center on methods for detecting and tracking blood-based protein biomarkers for various cancers.

The project will focus initially on building assays for quantifying existing protein biomarkers linked to tumor angiogenesis with the aim of using them for monitoring the efficacy of chemotherapy, said Mary Lopez, director of Thermo Fisher's Biomarkers Research Initiatives in Mass Spectrometry (BRIMS) center – which is leading the company's side of the collaboration.

Beyond developing assays for these existing markers, the parties also aim to identify new markers, both for tracking treatment efficacy and for early detection of cancers including breast and prostate cancer.

The work will be led by Tufts School of Medicine researcher Giannoula Lakka Klement, with whom, Lopez told ProteoMonitor, BRIMS scientists have completed a small pilot study to define the set of markers for which they plan to build the initial assays.

The goal is to develop complete mass spec workflows for protein quantitation that can be implemented on instrumentation installed at the Genesis Research Institute laboratory adjacent to the Newman-Lakka Institute, Lopez said.

"The plan here is to not do any routine work at BRIMS," she noted. Rather, the collaborators will "install the complete workflow at the [Newman-Lakka] site and then work with [the Newman-Lakka team] in the development of the assay and help them to implement it and deploy the [mass spec] technology there where they will be doing the routine measurements."

Lopez added that, if the biomarkers and mass spec assays prove successful, the Newman-Lakka team would likely pursue implementing them at several partner sites around the world.

At the American Society of Mass Spectrometry meeting this month, Thermo Fisher released two new triple quadrupole instruments – the TSQ Endura and TSQ Quantiva (PM 6/14/2013). Lopez said, though, that for now the company would be sticking with its older TSQ Vantage model for the routine quantitation portion of the Newman-Lakka collaboration.

"The Vantage is a very established system that we already have at BRIMS, and so we feel comfortable implementing that workflow there and evaluating it," she said. She added that the markers comprising the initial panel were "fairly medium abundance" proteins, and so measuring them would likely not require the heightened sensitivity of the Quantiva, which Thermo Fisher has advertised as offering a 10-fold sensitivity increase over the Vantage.

Another key ASMS release for the company was its Orbitrap Fusion Tribrid machine, which combines a quadrupole for precursor selection with both an Orbitrap and ion trap mass analyzer (PM 6/14/2013). Lopez noted that BRIMS researchers have been involved in developing and evaluating new applications for this instrument and are currently in the process of integrating it into their discovery workflows. At least at the outset, though, she said, her team plan primarily to use the company's Q Exactive for the collaboration's discovery work.

Initially, we'll be focused on using the Q Exactive, but moving forward we will probably use the Fusion to look at some of the samples and evaluate what kind of workflows it would be optimal for," Lopez said. "We are going to start with the Q Exactive and the Vantage and then move toward the Fusion and Quantiva."

The researchers will also be using Thermo Fisher's Mass Spec Immunoassay, MSIA, technology – an immunoenrichment technique designed to improve the sensitivity of mass spec workflows for improved quantitation of low-abundance markers.

According to Lopez, the initial angiogenesis panel the collaborators will work on consists of around six or seven proteins. While this size panel is theoretically within the multiplexing capabilities of an immunoassay platform, Lopez said the Newman-Lakka researchers have turned to mass spec due to the limitations of antibody-based approaches.

"They wanted to be able to look at the levels of this collection of markers in a single multiplexed assay that would give them very good quantification, and they were not able to do that with immunoassays," she said.

She added that by building the assays on a mass spec platform the researchers would be able to add additional assays fairly quickly if they were to discover new protein markers.

The mass spec system the collaborators plan to install at the Genesis Research Institute will enable moderate levels of throughput, Lopez said, noting that this would be sufficient for the Newman-Lakka team's current needs.

"They could have the capability to do maybe 100 samples a day if they wanted to," she said. "Obviously, that could be scaled up. I don't foresee that that will be needed for a while. They don't have thousands and thousands of samples coming in."

The researchers will work specifically with platelets as their sample source, which offer the advantage of being enriched for the angiogenesis-linked proteins under investigation. This presents a challenge in terms of working out protocols for normalizing the quantity of proteins present per set number of platelets, Lopez said, but, she added, "it's really very similar to doing assays on cell lysates."

"There is some precedent," she said. "So, I think it will be something we can implement fairly quickly, especially with this known panel, and then we will add to that panel as the work goes on."