A new approach developed by researchers from MIT and the Broad Institute of MIT and Harvard has made it easier to detect circulating tumor DNA in blood samples. Tumors constantly release DNA from dying cells, which briefly circulates in the bloodstream before being broken down. Blood tests have been created to identify this tumor DNA, aiding in cancer diagnosis, monitoring, and treatment selection. However, the amount of tumor DNA present is usually very small, making it challenging to develop sensitive tests to detect it.
To address this issue, the researchers developed injectable molecules called priming agents that temporarily slow down the removal of circulating tumor DNA from the bloodstream. The team created two types of priming agents, which, when tested on mice, significantly increased DNA levels. The percentage of detectable early-stage lung metastases rose from less than 10% to above 75% with the use of these agents. This new approach enables earlier cancer diagnosis, more sensitive detection of tumor mutations for personalized treatment, and improved cancer recurrence detection.
The priming agents can be administered an hour prior to a blood draw, effectively enhancing the visibility of tumor DNA. According to Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT, and a senior author of the study, this means that more DNA molecules can be collected for liquid biopsies, regardless of the purpose. Bhatia believes that this innovation will benefit all patients undergoing liquid biopsies.
Liquid biopsies are currently used to detect small quantities of DNA in blood samples for cancer patients, but with increased sensitivity, these tests can be extended to a larger patient population. Previous efforts to improve the sensitivity of liquid biopsies focused on the development of new sequencing technologies after blood is drawn. However, the researchers thought of a new approach that involves increasing the amount of DNA in the bloodstream before collecting the sample.
The body utilizes two primary methods to eliminate circulating DNA from the bloodstream. One is the presence of DNases, enzymes that break down DNA, and the other is through immune cells known as macrophages, which uptake cell-free DNA as blood passes through the liver. The researchers developed a monoclonal antibody to bind to circulating DNA and protect it from the DNases, preventing their degradation. They also created a nanoparticle that blocks macrophages from taking up cell-free DNA. This nanoparticle distracts the immune cells, allowing the DNA concentration to increase in the blood sample.
The priming agents were tested on mice that received cancer cell transplants known to form lung tumors. The results showed that the priming agents increased the amount of circulating tumor DNA recovered from the blood sample up to 60 times. Once the blood sample is obtained, sequencing tests can be conducted to identify tumor DNA and determine the type of tumor and potential treatment options.
Another potential application for the priming agents is early cancer detection. When mice were given the nanoparticle priming agent before blood was drawn, circulating tumor DNA was detected in 75% of mice with low cancer burden. Without the priming agent, no DNA was detectable. This potential breakthrough addresses the challenge of the scarcity of circulating tumor DNA in blood samples.
After the injection of either priming agent, DNA levels increase in the bloodstream within a couple of hours and return to normal within 24 hours. This means that patients can receive the priming agent, have their blood drawn, and undergo testing in a single visit to the doctor’s office. This quick turnover time is promising for future clinical use.
To further develop this technology, the researchers have launched a company called Amplifyer Bio, with the goal of advancing to clinical trials. Liquid biopsies are more accessible and less invasive than traditional screening methods for cancer, such as colonoscopies or mammographies. According to Bhatia, if these tools prove to be predictive, more patients can benefit from earlier cancer interception and improved therapy selection.
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1. Source: Coherent Market Insights, Public sources, Desk research
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