At the annual meeting of the Association for Molecular Pathology this week, the University of Miami's Richard Cote spoke about his group's development of a membrane microfilter device for the capture and characterization of circulating tumor cells from blood.
CTCs have potential for assessing disease progression and a patient's potential for metastasis. They can also help clinicians monitor therapeutic efficacy, and determine need for systemic therapy, and make prognoses about survival and recurrence. They're not merely cells that are being shed from primary tumor, but are a selective population of cells that have proliferative properties to be able to create metastases, Cote said. It's been shown that serial CTC counts predict survival in prostate cancer, and can present clinicians with a rapid way to determine if therapy is working, faster than any other methods like PSA testing or imaging.
However, it's difficult to capture these cells in blood. In essence, Cote said, asking technology to capture CTCs is asking it to detect a very rare event. In order to both find and then characterize the cells, single-cell detection and analysis is required. There are several platforms now in place to capture CTCs, but they rely on finding the antigens attached to CTCs, and this is a problem because some cancers don't express antigens, and those that do are very heterogeneous, Cote added. In addition, while some CTCs may be captures, many are not, leading to an erroneous picture of what's going on with a given patient's cancer.
So Cote and his team took a different tack. It's been known for more than 50 years that the size of solid tumor cancer cells is bigger than normal cells in blood. The difference is not big — only a few microns — but it is consistent. With that in mind, Cote's team developed a membrane with a very specific pore size, shape, and distribution, built to let smaller cells pass through, but to keep the larger CTCs trapped. When Cote evaluated the filter in a model system, he found the recovery rate of CTCs to be about 90 percent, in a process that takes less than two minutes.
In addition, the filter is made from a high-strength, optically transparent material. So the capture platform then turns into an analysis platform as the researchers don't even have to collect the cells from the filter — and risk losing a few — in order to characterize them. Multiplex immunohistochemistry can be done on the filter in order to determine the biological characteristics of the cells, se markers they may contain, and determine what their presence indicates for the patient.
The filter is currently being tested in trials, Cote said, and he hopes that eventually it can also be used to test biological samples other than blood, like urine.