Innovative immunotherapy treatments are one of the newest ways to treat cancer. They have been shown to dramatically affect outcomes and beat the disease, but unfortunately, the treatments don’t work for everyone. Scientists are working hard to try and determine why certain patients respond and why some don’t. An experimental urine test that could help this process has just received a major funding boost; the test will allow doctors to detect immunotherapy effectiveness very early on. This will allow doctors to adjust treatments for patients so that cancer can stop evading them.
The National Institutes of Health (NIH) granted $1.8 million to a research project at a Georgia Institute of Technology where Gabe Kwong has established a platform to discover complex disease and immune activity. The new funding from the NIH’s National Cancer Institute will be used to further Kwong’s research in evaluating immunotherapy progress. The platform works by using an intravenous injections of “activity sensors,” nanoparticles that detect enzyme activity of the immune cells attacking cancer. Once the sensor confirms the attack, there is a fluorescent signal in the urine.
In the past, cancer has been known to thwart treatment by either evading it from the start or simply ceasing to respond to treatment that has previously worked in the patient. This means that progress must be continually monitored since early resistance to therapy looks very different from later resistance. The particle that Kwong’s lab has developed will monitor the process the entire way through.
“We need to be able to classify different forms of resistance, so we can combat them better,” said Kwong, who is an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
Kwong plans to use the sensing technology to profile the subtleties in the treatment resistance. The advantage of his test over other tests currently on the market is that it looks for signals that come earlier in the process rather than later. A later signal is something like dead cancer cells shedding their DNA into the bloodstream.
Kwong states, “These tests can be quite effective, but some issues limit them, particularly in early detection: You have five liters of blood. Whatever the cells shed gets diluted significantly in your bloodstream.” That makes these signals harder to detect in blood tests. “Our sensors’ signals get concentrated in the urine, so, not only are they not diluted in the blood, but we usually see a hundred-to thousandfold signal enrichment,” said Kwong.
The sensors, which are biocompatible nanoparticles, have already been developed, refined as a reliable platform, and engineered with variations that experimentally sense blood clots, liver fibrosis, organ transplant rejection, and cancer. Kwong stated that in the end, he hopes to “expand the platform to detect most all major complex diseases and progress in treating them.”
How exactly does the urine test work?
The sensors are nanoscale balls that have bristles made of short amino acid strands with fluorescent “reporter” molecules attached to their tips. The sensors will gather in the compromised tissue like cancer. Immunotherapy uses T cells that secrete an enzyme called granzyme, which severs target amino acid strands in the cancer cells, triggering their death. The bristles that are attached to the sensors mimic the granzymes and cut off the bristles at the same time. “That releases the reporter molecules, which are so small that they easily make it through the kidney’s filtration and go into the urine,” said Kwong. Once the urine leaves the body, the fluorescent color is analyzed to see how well immunotherapy attacked the cancer.
“Many patients, especially those with solid tumors, are not responding to this treatment,” Kwong said. “The non-responders need to be detected very quickly.” The experimental sensor is important because it can give a clearer picture of how effective a current treatment is rather than traditional methods that may be less accurate or misleading altogether. One example is the measurement of tumor shrinkage. In some cases, T cells can cram into a tumor making it swell. This will lead some doctors to abandon the treatment that may seem like it isn’t working, when in fact it is actually very effective. The importance of the urine test is that it does not measure size, it measures activity.