The FLEXMAP 3D® supports high-throughput discovery of autoantibody biomarker candidates
Peter Schulz-Knappe is the Chief Scientific Officer at Protagen AG, based in Germany. Protagen is using Luminex’s FLEXMAP 3D® as part of its SeroTag® biomarker identification and development platform to create assays to support the development of drugs and companion diagnostics.
When developing your protein arrays, what challenges did you face?
Protagen had developed its own protein arrays for biomarker discovery, which allowed us to look at up to several thousand proteins at any one time. However, we felt that the data quality and reproducibility just weren’t high enough for the standard of research we wanted so we had to look for other technologies.
How did Luminex attract your attention?
Luminex had developed a new multiplexing platform, the FLEXMAP 3D, which allowed researchers to look at 500 different analytes simultaneously. We carried out experiments that compared our techniques to the Luminex technology, and we found it gave us data of much higher quality, higher throughput, and speed, and improved the reproducibility of results. The dynamic range was also much better, and the results were quantitative as well as qualitative.
Also, at Protagen, we used typical planar microarrays in batches of 100, which meant that a study of a thousand patients needed ten different batches. As the FLEXMAP 3D system could process up to 2,000 patient samples per batch, with up to 500 data points per patient sample, we could eliminate batch-to-batch variability, meaning that we could be much more confident in our results.
Were there any challenges in the switch?
We decided to shift completely to the Luminex system. It was a nerve-racking move, as everyone had to adapt to the new techniques and it left us wondering about all of our existing data and patents, which were based on the old technology. But we took the step, and bravely decided to re-run all of our existing patient samples. The resulting data clearly mandated us to amend all of our patents, and we believe that they are much more defensible now.
Our research requires up to 8,000 data points per patient sample so, with the FLEXMAP 3D system, we still have to run a number of assays per patient, but because data quality and reproducibility are so high, we continue to see a huge benefit.
What difference did the shift to FLEXMAP 3D make?
Precision medicine demands biomarkers that can move from the bench to the bedside by transforming biomarkers into in vitro diagnostics. Luminex technologies are available worldwide, and they are already used in a wide range of FDA cleared, diagnostic tests. This means that developers of diagnostic assays can stay with the same platform for discovery, validation, clinical testing, and commercialization while maintaining their line of evidence. It also makes it easier for third parties to be able to reproduce the results, for example, during clinical trials.
How have you applied FLEXMAP 3D to your research?
Our SeroTag biomarker identification and development platform uses Luminex’s xMAP® Technology for high-throughput discovery of biomarker candidates by measuring the levels of autoantibodies in serum samples from thousands of patients. We screened samples from people with autoimmune disorders and used the outcomes to create NavigAID SLE, a multiplex assay that uses biomarkers to separate and define subgroups of patients with systemic lupus erythematosus (SLE). NavigAID SLE can help drug companies develop more effective therapeutics for patients with SLE through precise disease characterization, patient stratification, and response prediction.
Last year, we also launched our first in vitro diagnostics based on the SeroTag platform. Compared with the ten-plus years that it usually takes to move a biomarker assay from concept to the market, these projects have only taken around three and a half years to this point. Our Multilisa® SLE multiplex assay will incorporate up to 10 standard markers and up to five autoantigens for SLE and will act as the proof-of-concept for our approach. We are also developing NavigAID SSc for Systemic Sclerosis, NavigAID SjS for Sjögren Syndrome, and Multilisa RA for rheumatoid arthritis. Many markers are in assay development, with consecutive launches expected this year. These products will validate both our approach and Luminex’s technology.
We are also looking at other disease areas, including cancer. Patients who are treated with immuno-oncology drugs, such as checkpoint inhibitors and cancer vaccines, can develop immune-related problems which move them into our field of expertise. Here we have a substantial collaboration with the National Cancer Institute to identify biomarkers that can be used to predict therapy responsiveness, monitor patients receiving immunotherapies, and detect adverse events early. These will be useful both in drug development and as companion diagnostics.
Want to learn more about the FLEXMAP 3D? Watch this video:
SeroTag and Multilisa are registered trademarks of Protagen AG.
Interview excerpted from Nature Inside View Advertorial published 1 June 2017.
Luminex supports life science research with its Research Use Only (RUO) product portfolio. Not for use in diagnostic procedures.