Corning, the glass and ceramics giant, is looking to move its Epic system more aggressively into the label-free space because it sees this as a market with significant potential for growth, a company official said recently.
Corning discussed its intentions as an increasing number of drug makers explore possible applications for label-free screening platforms and seek to learn more about the technology, the official said.
Over the next two to three years, “our primary interest is showing researchers the benefit of this technology, and seeing it adopted in more applications,” Ron Verkleeren, business director for the Epic system, told CBA News this week.
Corning’s Epic is a label-free technology platform that is designed to perform both biochemical and cell-based assays, including signal transduction, cytotoxicity, cell proliferation, and lipid signaling. Among its principal rivals are MDS Analytical Technologies’ CellKey system and SRU Biosystem’s ComBIND.
“We have quite a lot of depth in materials and optics, and we think that there are going to be a lot of exciting applications and new products [that exploit] our depth in those areas to solve tough problems in biology and the life sciences,” Verkleeren said.
To that end, Corning plans to introduce more products in the label-free space, and “we think that it has enormous potential to change how drug discovery is conducted,” said Verkleeren.
A specific advantage of the label-free approach seems to be that because it’s a universal readout, an assay can be developed quickly, Lance Laing, a scientist at SRU Biosystems, told CBA News. “When we are working with customers, they are pretty surprised that we can get a result within a few hours — they are used to spending months to develop an assay,” he said.
Taking a label-free approach also means that researchers can see all the interactions that are going on in an assay. “It turns out that the cell response to chemical stimuli is quite complex, and involves looking at the many ways that the cell is responding to the stimuli, and those responses can be parsed out and identified,” said Laing.
“We, like everyone else, are still learning,” said Ralph Garippa, a research leader at Hoffmann-La Roche, which uses the Epic platform in its drug discovery work. “We are fascinated with the early results [of GPCR assays run on the Epic].”
For instance, the label-free data from these GPCR assays are giving his group new information on transfected receptors in proteins that they can put into immortalized or clonal cells. The data are also yielding new information on endogenous receptors and protein targets in cells — ones that they do not have to transfect into native cells.
“As a matter of fact, [the Epic] may give us a better context in which to study these targets,” Garippa told CBA News.
“It also creates possibilities for us to look at stem cells or primary cells or immortalized cells in a new context,” said Garippa. “Our plans right now are to learn as much as we can about the technology to see how it fits into our drug-discovery program.”
Garippa added that some groups are looking at label-free technology for cytotoxicity research because of its ability to detect morphology changes and protein translocation changes.
“Right now, the jury’s out,” he said. “But we are fascinated with the possibilities of using these experiments to obtain information that we could not obtain previously, or that we could only obtain by running several assays in parallel, and then integrate the data in order to get a characteristic picture.”
Verkleeren made his comments after Corning held a two-day summit last month near its Corning, NY, headquarters on the use of label-free technologies in drug discovery.
“We wanted to have a forum where some of the leaders in the industry and in the field of label-free technology could get together and discuss their most recent results and information,” Verkleeren said last week. Participants included GlaxoSmithKline, AstraZeneca, Johnson & Johnson, Cornell University, Johns Hopkins University, and Yale University.
Label-free technology “is really changing the way drug discovery is conducted today.”
One of the goals of the summit was to reach some conclusions about the technology and where it is headed, and what the implications are for its role in drug discovery, Verkleeren told CBA News.
He said the summit reached three main conclusions: That follow-up studies to some initial screens conducted earlier, and presented at last June’s Society of Biomolecular Sciences symposium on label-free technologies, showed that label-free technology has the ability to find novel compounds with novel activity that cannot be identified with assays that only look at one molecule and one pathway.
The second conclusion was that “two camps are beginning to form” in the industry. One camp believes that “since label-free technology has the ability to see the entire cell assay response, maybe you should start by first performing all screens with a label-free technology, and understand the compounds that show activity further.”
The second camp believes that label-free is a great orthogonal technology that can be applied more efficiently to reach a conclusion or identify a very robust set of compounds for advancing hit-to-lead programs, he said.
The third conclusion was that “label-free could open the potential for performing drug discovery in a slightly different way,” Verkleeren said.
Several presentations at the summit were from academic leaders and suggested that scientists may be able to use label-free technology for systems-biology approaches to drug discovery, so label-free technology “is really changing the way drug discovery is conducted today.”
Take GPCRs, for example. “Historically, most GPCR assays have been run in a reductionist manner, looking at a single signaling readout, such as calcium influx, cAMP, or ERK translocation,” said Roche’s Garippa.
However, with the Corning Epic system, as well as with other cell-based label-free systems, “we are fairly confident that we are looking at the integration of the sum of the cellular events that are produced after a drug binds to its receptor on a cell surface,” he said.
Garippa said he feels such information can be very enabling if “we learn how to interpret it, because right now the field is rife with the thought of functional selectivity around GPCRs.” He added that a whole spectrum of downstream events occur after a small molecule or antibody binds to a seven-transmembrane receptor, and those effects can be quite varied if a compound stabilizes a certain transmembrane confirmation to, for instance, full agonism, partial agonism, neutral antagonism, partial-inverse agonism, full-inverse agonism.
What investigators are observing from these cell-based assays are deflections that represent either the attachment strength of the cell to its substrate, a change in morphology of the cell, or a change in the intracellular proteins within the cell.
“These are events that we could not really track before in a fully integrated manner, but now label-free cellular assays are allowing us to do that,” Garippa said.
Another key trend is that without having to identify an antibody to a target protein, or a specific dye to that protein or cellular compartment, or without introducing a fluorescent protein, one can simply grow cells on the optical or microelectrode-based plates, and get a baseline read, said Garippa.
Cells can then be stimulated with a pharmacological agent, and investigators can look for a response. That response can be interpreted on its own, or one can attempt to match the signature with a response that’s given in that cell with a known drug.