In a collaboration that could signal an emerging application area for high-content cellular analysis, Cellumen said this week that it is working with the Mayo Foundation for Education and Research to apply its cellular systems biology profiling approach to the stratification of breast cancer patients for clinical trial enrollment.
The goal of the project is to improve diagnosis and treatment for personalized medicine — a potentially new market for high-content technologies, which have traditionally been limited to efficacy and toxicity testing in drug discovery.
Financial details of the agreement were not disclosed. Cellumen CEO Lans Taylor declined to discuss the financial aspects of the agreement or to speculate on the size of the market for cell-based diagnostic and stratification tests beyond stating that the market for such technology would be “huge.”
The goal of the project is to develop a test that would be more powerful than existing methods that could be used for both patient stratification and as a diagnostic tool to improve treatment selection.
Taylor said the project has a timeline of two years.
A Systemic Approach
Cellumen is working with Mayo to create panels that combine breast cancer biomarkers and migratory immune cell biomarkers using multiplexed fluorescence that can be applied to patient cells and tissues. Currently, a retrospective study is underway to correlate these biomarker panels with outcomes using traditional pathology.
Taylor told CBA News that the biomarkers in the panels are drawn from an “evolving list” of potential cancer cell biomarkers that have been identified in previous studies.
“An important twist that we are adding to it is that we look at a tumor, in this case breast tumors, as ‘a system within a system,’ ” Taylor said. “In other words, within the system of the patient, there is another system, the breast tumor system.”
That system contains a combination of normal cells, cancer cells at different stages of genetic evolution, and migratory immune system cells, said Taylor, noting that an important question in cancer research today is whether the immune system sees the tumor cells as “self” or “non-self.”
“Until recently, the assumption has been that the heavy predominance of migratory immune cells in tumors was evidence of the immune system attacking the cancer,” said Taylor.
However, he said, new evidence indicates that, depending on the cancer, the immune system may actually be responding to the cell death that occurs as tumors grow. Taylor explained that the immune cells are being encouraged to come in and save cells from dying.
The whole approach, said Taylor, is to treat the tumor as a system, and use a set of functional biomarkers — both cancer cell biomarkers and immune cell biomarkers. “We think that combination, heavily multiplexed, will give a powerful fingerprint concerning the state of the disease and the prognosis,” he said.
The phenotypic profile of a patient’s tumor will influence the choice of treatment, said Taylor.
He said that Cellumen and Mayo are using the retrospective study to build and optimize the cellular biomarker panels. After that, he said, the partners plan to conduct a prospective study.
Full of Potential
Taylor said that such a test could be used to evaluate biomarkers for other cancers or even other types of diseases, but the decision to start with breast cancer was based on several reasons — not least of which was the fact that breast cancer is well studied and there is “a fair amount of genomic and proteomic data about it already available.”
He also said that the Mayo and Cellumen teams feel that existing tests, which are based on cellular genomics and proteomics, could be improved upon by taking this cellular systems biology approach.
Taylor said that Cellumen plans to work with other partners to develop similar tests for other cancers, but declined to comment further.
“I think that this is one of the first uses of high-content in biomarker analysis.”
The Mayo Foundation could not respond to requests for comment before the CBA News deadline.
High Content Takes Off
The collaboration between Cellumen and Mayo is a sign that high-content technology is coming into its own, according to some observers.
“I think that this is one of the first uses of high-content in biomarker analysis,” said Mark Collins, marketing manager for cellular imaging at Cellomics. He added that he thinks the field will continue to move deeper into personalized medicine and other emerging areas within drug discovery and development.
“At first, people were doing relatively simple things and were not making the best use of [high-content screening’s] multiparameter, multichannel capabilities,” Collins said.
However, as software and hardware has improved over the last about two years, he noted that Cellomics has seen its customers do “interesting things” with high-content, and more and more, they are looking at the phenotypic effects of compounds and profiling.
“And the cool thing is, you’ll be able to feed that data back to discovery to design even better compounds,” he said.
Marcel Bally, head of advanced therapeutics at the BC Cancer Agency in Vancouver, BC, told CBA News that in the past, some researchers had taken tumor cells from patients and then tried to determine their sensitivity to drugs in vitro using cell-based assays, with the goal of trying to identify the drugs that would be most effective against specific diseases.
However, “With HCS, we may be able to do that a little bit more effectively because we will be able to look at more things. We can measure more parameters and get away with using fewer cells,” he said.
Currently, phenotypic profiling is an interesting academic use of high-content analysis, Bally said. “The trick now is whether or not one can actually validate the information.” If an assay is going to be used clinically, you need to be sure on some level that you are using a robust system, he noted.
He added that many imaging assays are not that robust, and it requires a lot of effort to get them to the point where they are fully validated for clinical use.