Paper-based test may have ‘huge potential’ identifying, managing leptomeningeal disease
Key takeaways:
- UCLA researchers are working on a paper-based test to identify leptomeningeal disease.
- The test would quantify the number of cancer cells in cerebrospinal fluid, which could help guide treatment.
A few years ago, UCLA organized a think tank between its neurosurgery and bioengineering departments.
Daniel Kamei, PhD, professor of bioengineering at UCLA Samueli School of Engineering, remembers it as the first time he ate with nonfamily members since before the COVID-19 pandemic began.
“I still remember wearing my mask to the event,” he said.
Kamei also remembers that gathering as the day he met Won Kim, MD, neurosurgical director of the brain metastasis program at UCLA.
Together, they have begun work on a paper test that could diagnose and evaluate treatment of leptomeningeal disease within hours.
“Ideally, when the patient goes in to see the physician and they take out the cerebrospinal fluid, a hospital staff person will take that fluid and apply it to our diagnostic and get that information in real time,” Kamei said.
‘We’re losing critical time’
Individuals who develop leptomeningeal disease — cancer that has spread to the cerebrospinal fluid — have a median survival of just 4 months, Kim said.
Diagnosing the disease takes significant time, too.
Patients get a lumbar puncture to test for the cancer if they have neurologic symptoms, such as facial weakness or numbness, difficulty swallowing or hoarseness.
“You do the lumbar puncture, and it takes maybe 5 days for those results to come back,” Kim said. “But the sensitivity is only 50% with the first lumbar puncture, so you do another one, and it increases to 75% [or] 80%. You do a third one of the same patient [and] it gets to the 90% range. To have a test be so insensitive to such an important problem, and to establish a diagnosis over 2 to 3 weeks, you can see how we’re losing critical time.”
Progress report
Kamei has worked in the point-of-care space for years, but he has not had much interaction with cancer diagnostics.
“Having a paper test be used for cancer is something that’s always had a huge activation barrier because people would rather use lab-based tests,” Kamei said. “But here’s an application that Dr. Kim found where, because time is of the essence, using a paper-based test becomes really applicable for this important disease.”
Kamei and colleagues have been working on a paper-based test for leptomeningeal disease for about half a year.
They are trying to detect the epithelial cell adhesion molecule on the surfaces of breast cancer cell lines.
“We’ve been able to detect these breast cancer cells at really low concentrations,” Kamei said. “It requires some sample processing in order to do that, but that has been very exciting to see.”
The amount of circulating tumor cells in cerebrospinal fluid can vary dramatically.
A prior study showed the median value to be approximately 30 cells per mL, Kamei said. They have been using that figure as their guide.
“We’re trying to get it down to that point,” Kamei said. “Sometimes we are able to do so, and sometimes we’re not, but it’s close. I think that’s promising, but this is all in the laboratory with spiking these cells into a solution. It still needs some work.”
The test also is being designed to determine the quantity of cells in a sample, which could help clinicians identify how patients are responding to treatment.
Currently, lumbar punctures can only determine if circulating tumor cells are present. There are no standard ways of reporting the quantity of cells.
“What makes Dr. Kamei’s technology groundbreaking is that it will be able to quantify the number of cells that are there and then color code them based on that quantity,” Kim said. “A physician can say, ‘This is a blue signal. It has this X number of cells,’ or ‘It’s red. It has X number of cells.’ That’s the way we hope to actually demonstrate a response to treatment. Right now, all we can say is, ‘Yes, you have cells,’ or, ‘No, you don't have cells.’ That’s a very poor way of tracking response to treatment.”
Kamei and colleagues also are examining whether multiple lines can be printed on the paper test to determine quantity.
“We’re attacking this in multiple ways,” Kamei said.
‘Huge potential’
Kamei said they would like to be evaluating patient samples within 2 years.
“After optimizing the tests with cancer cells in buffer, we will test with synthetic cerebrospinal fluid, and then eventually test with patient samples obtained by Dr. Kim,” Kamei said.
These tests would not be for at-home use, like COVID tests.
“A staff person at the hospital will actually perform the test, which gives us a little bit more leeway in what can be done as far as the user-handling steps,” Kamei said.
The technology being developed is a platform technology where the antibody can be changed to detect for any cancer type.
Kim said these tests have “huge potential.”
“It could be very useful and really change how we detect and treat leptomeningeal disease,” he added. “I'm very excited about it, too.”
Reference:
- Study seeks rapid, paper-based test to detect cancer cells in cerebrospinal fluid (press release). Available at: https://www.uclahealth.org/news/release/study-seeks-rapid-paper-based-test-detect-cancer-cells. Published Oct. 17, 2024. Accessed Nov. 13, 2024.
For more information:
Daniel Kamei, PhD, can be reached at kamei@seas.ucla.edu.
Won Kim, MD, can be reached at wonkim@mednet.ucla.edu.
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