Originally posted: October 30, 2008 By Tony Fong GenomeWeb ProteoMonitor
CAMBRIDGE, Mass. — With its technology-development programs well under way, the National Cancer Institute’s Clinical Proteomic Technologies for Cancer initiative has begun turning its attention to the big vendor community.
Its aim is to get those companies tools into the research community and to invest big commercial players more heavily into CPTC’s efforts, its director, Henry Rodriguez, told ProteoMonitor this week.
When it was created two years ago, CPTC initially focused on boot-strapping its three programs directed at technology development: the Clinical Proteomic Technology Assessment for Cancer, the Advanced Proteomic Platforms and Computational Sciences, and the Proteomic Reagents and Resource Core.
But as these programs have enabled materials, such as antibodies, reagents, and protocols, to begin making their way into the CPTC’s pipeline, the organization last year began to shift its emphasis to also include vendors. The initial target was smaller shops and at its second annual meeting, held here this week, some of the results from that effort were highlighted as a number of small proteomics companies presented technology developed with funding by CPTC.
Now, the push will be directed at the larger commercial vendors, Rodriguez said.
“We tried to emphasize the private-public partnerships” at this meeting, Rodriguez said. “Even though we’re producing the science, we’re also producing materials as a program. … And while we give them back to the community, it quickly dawned on us that the community may already have some platform that is commercially sold.
“So we said, ’Let’s put out solicitations now to the small-business community with these platforms and at the same time, if they’re successful, they will start to adopt the reagents that we’re developing and that could go back to the community,’” he said.
To do so, his office last year worked with NCI’s small-business office to issue a solicitation to encourage small businesses to adapt their own platforms to techniques and methods developed by the CPTC, and to use materials produced by the CPTAC group.
The result can be seen in work performed by, for instance, Allele Biotechnology in San Diego, which used a Phase 1 SBIR grant from the NCI to develop a panel of antibodies with high affinity and specificity against 10 cancer-related antigens, company CEO Jiwu Wang said during a presentation at the CPTC conference. The antibodies, he said, can be formatted to be specific to mice, rabbit, and other model organisms, or be developed into full IgG antibodies.
Improving MS Capability
Now as the CPTC shifts its attention to larger vendors, much of its attention will be directed at mass spectrometry. CPTAC, which comprises five teams and a host of collaborators, is in the process of publishing three papers on work it has done studying reproducibility with mass spectrometers [See PM 09/04/08]. When those are published, CPTC anticipates hosting a teleconference with the major mass-spec vendors “to say to them, ‘Here are the things that we’re producing that add a lot of value. What are the needs that you have … that either we are addressing that we can work with you, or that we’re not addressing to see if we can also build that into the program?’” Rodriguez said.
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“What we can bring to [the table] is to say, “Here’s a program with this network. It doesn’t focus on one platform, but we recognize that universally, across them all, we can develop some very nice metrics that add not just [an] advantage to one … but advantages across the board.’”
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Even before CPTC was created, NCI met with mass-spec vendors to get their views on what such a project could do for that community. What the agency heard, for example, was that manufacturers needed help in improving, from a computational approach, their instruments’ detection and identification capabilities, Rodriguez said.
To be sure, each vendor has its own R&D personnel working on such problems, but CPTC offers a greater breadth of researchers working on methods to improve the instruments, Rodriguez said, citing work by Richard Smith at Pacific Northwest National Laboratory.
At the two-day conference, Smith presented research being done by his lab on a high-throughput platform based on a liquid chromatography coupled with an ion mobility spectrometer that is in turn interfaced with a time-of-flight mass spec. In addition to improved throughput, the platform offers greater sensitivity, robustness, and quantitative capabilities for biomarker discovery, verification, and preclinical validation, Smith said.
“What we can bring to [the table] is to say, ‘Here’s a program with this network,’” Rodriguez said. “It doesn’t focus on one platform, but we recognize that universally, across them all, we can develop some very nice metrics that add not just [an] advantage to one … but advantages across the board.”
CPTC also plans to meet with the major reagent vendors in order to get them into the fold, he added.
No Discovery Work Here
CPTC is one of several federal initiatives and programs focusing on proteomics to tackle diseases such as cancer and neurological ailments, and to address biodefense issues. But unlike other federal efforts, CPTC is directed not at discovery work but at improving a proteomics scientist’s workflow: its goal is to provide solutions to challenges such as reproducibility, standards, and poor study designs that have hindered the field.
CPTC would like to take the technologies developed through its programs to other proteomics programs being funded by the NIH as well as other agencies, and say, “’Here’s a robust workflow, a methodology that we know can give you give you the power to identify where variability occurs, and if you can account for it, we’re there; if you cannot eliminate it, we can tell you how to best deal with it,’” Rodriguez said.
A more recent challenge in proteomics Rodriguez and others have identified is specimen quality, which can introduce biases into an experiment.
CPTC is focused on the analytical and pre-analytical aspects of research, but is also working with the NCI’s Office of Biorepositories and Biospecimen Research to overcome that challenge by developing common protocols for specimen collection and handling, Rodriguez said.
Papers and Antibodies Coming Soon
During the meeting, an update was also provided on CPTAC’s continuing work on mass-spec reproducibility. To date, the group has performed six studies, with the first looking at a 20-protein mixture and eight instrument types, and later studies steadily progressing to a more complex yeast-reference mixture and the use of ion trap mass specs.
With each progressive study, the group incorporated more refined standard operating procedures such as standardized chromatography and common statistical phase distribution.
While Daniel Liebler, who is heading the CPTAC team at Vanderbilt University, one of five CPTAC teams, declined to discuss in detail the findings from the studies, he said during a presentation that one of the deliverables from the research so far is that the yeast proteome potentially could provide a model for biomarker research via a shotgun proteomics platform.
The CPTAC teams are preparing three papers on their research: one describing their findings with the yeast proteome; another describing metrics that can serve as reference points for mass specs; and one describing the work they did looking at variability in peptide and protein identification between and across systems.
Finally, Tara Hiltke, program manager at CPTC, provided an update on its antibody initiative [See PM 11/29/07]. The antibodies resulting from its first funding round will become available to the public by the end of the year, she said. A third funding round to develop antibodies against about 40 antigens will be announced in January.
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