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Cellzome Wins $1.5M UK Grant for Work with Pfizer to Characterize Therapeutic Stem Cells

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By Adam Bonislawski

Proteomics firm Cellzome said this week it has won a two-year, €1.1 million ($1.46 million) grant from the UK’s Technology Strategy Board to support stem cell characterization work that the company has undertaken in collaboration with Pfizer, the University of Sheffield, and biotech firm Plasticell.

The project aims to identify protein markers predictive of deleterious changes in human stem cells intended for therapeutic use, and will use Cellzome’s Episphere and Kinobead chemoproteomics technology as well as mass spec-based proteome-wide screening, said David Simmons, the company’s chief scientific officer.

The aim, Simmons told ProteoMonitor, is to establish proteomics as the gold standard for characterizing therapeutic stem cells, a process that is currently dominated by genetic techniques like gene expression profiling and gene chip arrays.

“Our goal is, in the course of this two-year grant, to do sufficient numbers of analyses to generate a database that shows that proteomics is the way to characterize stem cells for therapeutic use,” he said, noting that the need for in-depth characterization is one of the primary regulatory concerns regarding stem cell therapeutics.

“For the regulatory agencies the biggest hurdle is safety, and the biggest thing the regulatory agencies want with stem cells is in-depth analytic characterization,” Simmons said. “We believe that [proteomics] could be the deepest and most robust way of [ensuring] that stem cells are what you think they are.”

“Our business goal is that this would be the method everyone would have to use to characterize stem cells for therapy, that we could lock it into the [Good Manufacturing Practices] protocols you’d have to use to get accreditation for putting [stem cells] into a human being,” he said.

The award follows stem cell research done by Cellzome with Pfizer’s Neusentis research unit earlier this year (PM 5/13/2011), and, Simmons said, is to an extent a validation of those efforts.

“What we’ve done over the last year is basically build up the robustness of our dataset in terms of reproducibility from week to week, run to run,” he said. “That was the first necessary part of this work because this was a new venture for us. We’ve never done any work in stem cells before.”

For the study, Cellzome has been using its Episphere and Kinobeads platforms, which allow for characterization of epigenetic and kinase targets, respectively. The company is also doing whole-proteome analyses, looking for protein markers outside the subproteomes in which it has traditionally operated.

Whole proteome stem cell characterization has seen significant activity in recent months, with both Joshua Coon’s lab at the University of Wisconsin-Madison (PM 9/16/2011) and Albert Heck’s group at Utrecht University (PM 12/2/2011) publishing proteome-scale comparisons of human embryonic stem cells and induced pluripotent stem cells.

While the Episphere and Kinobeads platforms are proprietary technologies, Cellzome’s whole-proteome characterization efforts are fundamentally similar to those used by those academic researchers, Simmons said. He suggested, though, that the company had an advantage over such labs in terms of doing this research on an industrial scale.

“We would say that we have a track record of industrialization,” he said. “We have a fleet of mass spectrometers running 24/7 that have been running for 11 years now and we have high-throughput data analysis. I think we’re more kitted out than most academic labs to do this on a semi-industrial scale, to do it quickly and actually lock it down into a [standard operating procedure], and run it as a business.”

Going forward the company plans to integrate the data generated via its whole- and sub-proteome analyses with additional functional data provided by its collaborators at Pfizer, Sheffield, and Plasticell, Simmons said.

These collaborators will be providing “a whole battery of functional analyses that are being generated on the same cells that we’re generating our proteome maps on,” he said. “Then what we’ll need to do is put all of that data together – the proteome maps with the cell functional data – to see how they correlate. This grant is basically to start that process.”

While Cellzome’s efforts to develop a proteomics platform for stem cell characterization are still in the early stages, clinical trials for stem cell therapeutics are underway. The first trial of human embryonic stem cell therapy in Europe received approval from the UK's Medicines and Healthcare products Regulatory Agency in September.

That trial, which is being conducted by Santa Monica, Calif.-based stem cell firm Advanced Cell Technology in collaboration with clinicians at London’s Moorfields Eye Hospital, aims to slow or reverse the effects of the eye disease Stargardt's macular dystrophy by injecting retinol stem cells into patients' eyes. It accompanies a similar trial at the University of California, Los Angeles, launched in July.

In October 2010, Menlo Park, Calif.-based pharmaceutical firm Geron launched the first ever therapeutic stem cell clinical trial, attempting to use the cells to restore neural function in patients with spinal cord injuries. It discontinued the trial in November, however, citing cost concerns and a narrowing of focus to its oncology portfolio.

Neither of these trials, Simmons noted, used proteomics approaches to vet the stem cells used, relying instead on existing methods. “We’re coming to the stage now with a new method to see if [proteomics] genuinely does give you better depth and more confidence,” he said. “I think the analytical methods we are developing are going to be key because all the regulatory hurdles aren’t over yet.”


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

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