Protein profiling chips made a high-profile appearance at the American Association for Cancer Research annual meeting in San Francisco this week: A total of 25 different poster presentations at the conference have featured research with Ciphergen Biosystems’ ProteinChip platform, which is based on Surface Enhanced Laser Desorption/Ionization technology, a technique where chemically coated chips capture proteins, often contained in serum or a whole blood sample, then mass spectrometry is used to map them.
This plethora of papers is unprecedented, according to Dick Rubin, Ciphergen’s director of marketing. “At the Philadelphia AACR meeting three years ago, we had four or five papers,” Rubin said, speaking from the Ciphergen booth at the exhibit hall of the conference. “Since then we’ve expanded in leaps and bounds.” Rubin added that the Ciphergen booth had been “inundated” for the first few days of the conference by new people wanting to get on the ProteinChip bandwagon.
Meanwhile, Ciphergen rival LumiCyte, which also holds a license to SELDI, put its own spin on the protein profiling whirlwind this week, announcing that it had developed a SELDI-based system for mapping 1,500 protein ‘features’ at a time from a single serum sample.
This accomplishment, “represents a five-fold increase in the discovery potential” of protein profiling technology, as previous SELDI systems have only been able to profile 200-300 proteins at a time, said Lumicyte CEO William Hutchens.
The 1,500 features can be combinations of unique proteins and different post-translationally modified forms of a single protein, such as the unphosphorylated and phosphorlylated states. The ability to see these additional proteins and protein states “may have significance in terms of identifying biomarkers for disease states or signaling pathways associated with the onset of disease,” as protein modifications often play a role in the cellular disease process, Hutchens added.
This increased throughput could give LumiCyte a technological edge over Ciphergen: Ciphergen’s ProteinChip system can profile 200 and 800 proteins per assay.
Rubin hesitated to comment on LumiCyte’s technology — Ciphergen and LumiCyte are currently embroiled in litigation over the rights to SELDI technology — but then added that he would “wait to see the data” on the new LumiCyte system.
LumiCyte said it is not planning to publish any proof-of-principle studies on this new enhancement of its technology: “We have protein maps with in excess of 1,500 features. It’s a fact, not an observation that needs validation,” Hutchens said. The company is nonetheless planning to “clinically validate” its technology through collaborations with researchers to find disease biomarkers.
These disease biomarkers are an increasingly hot item, as the AACR papers show. The Ciphergen abstracts include papers finding potential protein diagnostic markers for ovarian, bladder, lung, breast, prostate, liver, esophogeal, and nasopharyngeal cancers, as well as cell death in tumor cell lines. Many of these represent work completed over the last two years.
Bao-Ling Adam, a research assistant professor at Eastern Medical School in Norfolk, Va., co-author on a poster that used Ciphergen technology to profile prostate epithelial cell tissue, said her lab began using Ciphergen protein profiling technology three years ago for biomarker discovery efforts. Now that the biomarker patterns have been identified, differentiating normal from pre-neoplastic and malignant cells, the group is working on identifying the proteins involved to see whether they are known or unknown diagnostic markers, and then will work to develop antibodies and immunoassays. “So far we are still in research mode, but we want to take [our work] to the next phase for clinical screening.”
Other researchers have already gone to the next stage, among them a group from Harvard Medical School and Brigham and Women’s Hospital in Boston that presented a poster on haptoglobin alpha chain, a novel biomarker for ovarian cancer uncovered with the ProteinChip system. The group showed that levels of this protein were elevated in the sera of a majority of women with ovarian cancer, and recorded 90 percent specificity and 71 percent sensitivity when using the haptoglobin peak as the diagnostic criterion, the scientists said.
Not everybody is so willing to share their results: Like LumiCyte, which says it has already identified new markers for prostate cancer diagnosis but has not revealed these markers, other users of the powerful SELDI technology are keeping their biomarkers to themselves.
“When you find an interesting new marker, it is such a hot piece of information that until it is published or a patent is applied for, people hold that information close to the chest,” Rubin said.