In a belief that “now it’s all about content,” protein array slide maker Schleicher & Schuell will unveil a 120-antibody array for serum biomarker discovery this weekend — and will follow with the release of a 1,200-antibody array in the fourth quarter of this year, S&S business development manager, Robert Negm, told ProteoMonitor.
The company will launch its 120-antibody array on June 5 at the American Society for Clinical Oncology meeting in New Orleans, and the array will be available for sale June 11. The array was co-developed with Stephen Hewitt, clinical investigator in the tissue array research program at the NCI. The release follows S&S’ January release of its first content array, Fast Quant, which contains antibodies to nine cytokines.
The new array will include 120 commercially available antibodies to known serum biomarkers such as CA125 and PSA, spotted in triplicate and detected using single-label fluors. It will be targeted toward those using SELDI and 2D gels to look for protein biomarker patterns, said Negm. Negm hopes that S&S will capitalize on two recent trends in biomarker discovery technology: make it cheap and easy to use, and make sure you know what you are looking at. With a price of $599 for a pair of two-pad pre-printed slides, “we feel pretty confident that this is going to be the most affordable proteomics tool available,” he said. As for identification, “If you try to compare this with SELDI, for example, what does SELDI give you? It gives you a pattern, and so does this product. It [shows you] which proteins in serum are up, and which are down. But in ours, you have a much stronger indication that you know that actual identity of the protein, whereas in SELDI you just get a pattern without any identification.”
The idea behind the chip is that biomarkers for a number of different cancers may be up- or down-regulated for one particular disease state. “We’re looking at the translational cancer researcher that wants to cluster or profile the abundance of biomarkers so that they can identify panels of serum biomarkers related to their particular disease,” he said. “So this chip will allow those scientists to identify a grouping of markers that might be associated with, say, early detection of prostate cancer or measuring the benefits of treatment of prostate cancer, or the likelihood of recurrence of prostate cancer, depending on what they study.” The chip allows for semi-quantitative ratiometric comparisons, which Negm emphasized are for research purposes only and will need to be validated separately before translation into a diagnostic.
But this type of chip cannot detect proteins that have not yet been identified as biomarkers, unlike SELDI. Negm’s answer to this is a massive — and rapid — scaling up of the content on his chips. “Every six months we’re going to version the product, and just add more serum protein-specific antibodies until essentially we end up with a chip that covers the profile or measurement of the entire serum proteome,” he said.
The first step in this process will be the 1,200-antibody chip that the company plans to release later this year. Problems with cross-reactivity usually associated with that level of density will not be an issue, according to Negm, due to the use of a small-molecule fluorescent-labeling system licensed from Amsterdam, The Netherlands-based Kreatech Biotechnology. The company will sell the labeling system separately from the chip itself, however, because some people “might be using Cy5 or Cy3 dyes from Amersham, and we don’t want to hinder or create a barrier for them to buy the product,” Negm said. Negm compared the Kreatech labels to those that Brian Haab, special program investigator at the Van Andel Research Institute, has been developing.
Haab told ProteoMonitor that “there’s no limitation on density by the labels or by the printing either,” with Kreatech’s labels and S&S’s slides, but that actually finding 1,200 good quality commercial antibodies — and validating them — would be another matter entirely. Haab was surprised to hear that S&S is planning to ramp up to 1,200 antibodies so quickly. “I don’t think they’re planning on doing those validations if they’re going to get it out that fast,” he said. Validation is desired, he said, because “some of the antibodies might not work that well in a microarray assay. Some of them might denature … you might get variable amounts of cross-reactivity with each one. So you have to have some plan for how you’re going to handle that data.”
Negm said that company is depending on the validations already performed by commercial antibody suppliers for the 120-antibody array. As for the 1,200, “we will validate the higher density chip prior to launch by demonstrating reproducibility of the abundance profile with sera from diseased individuals compared to serum from healthy controls,” he said. He added that he thought that reproducibly producing patterns was the most important thing for a research tool.
But Dolores Cahill, director of the Center for Human Proteomics at the Royal College of Surgeons in Dublin, Ireland, said that individual validation of every antibody is important even for research tools. “So really, if you were to do it even as a research tool, ideally they should compare each antibody on the chip with an ELISA for sensitivity and reproducibility,” she said. “Then you need to know … for each antibody, what are the detection limits, sensitivity and specificity, background noise and cross-reactivity.” She said that a sandwich antibody assay could also be done as a validation step. Cahill is involved in European efforts to produce a proteome-wide collection of antibodies (see PM 9-19-03).
While they were skeptical about the rapid release of a 1,200-antibody array, both Haab and Cahill said that S&S’s surfaces are among the better candidates for printing content arrays, and that a high-density antibody array is definitely in demand. “It’s the way to go,” Cahill said.
Negm was bolder. “I think that once a high density antibody array specific to cancer serum markers becomes available, people are just going to flock to it, because it makes sense,” he said.