Cancer has an unfortunate and often deadly tendency to spread through the body, and the most common location for secondary tumors to appear is the lungs. Now, scientists at Harvard’s Wyss Institute have developed a way to treat metastatic tumors in the lungs, by attaching immune-baiting drugs to red blood cells.
After a tumor takes hold somewhere in the body, it often begins to metastasize. Cancer cells break off the main tumor and circulate in the blood until they find a new home in another tissue, then form a new tumor there. Sadly, it’s common for patients to undergo surgery to remove their primary tumors, only to find out that it’s already spread.
Previous studies have shown that the lungs are one of the most common locations for secondary tumors to spring up. That’s because they’re full of tiny blood vessels where it’s easy for rogue cancer cells to become wedged, planting the seeds for new tumors. To further compound the issue, traditional treatments like chemotherapy are particularly damaging for lung tissue, making these metastatic tumors all-too-often deadly.
An emerging alternative is immunotherapy, which involves supercharging our natural immune systems to fight cancer. So for the new study, the Wyss researchers focused on delivering some of these immune-activating drugs to the lungs.
This study builds on earlier work in attaching drugs to red blood cells, which make almost perfect carriers. These ubiquitous cells are already circulating throughout the body carrying oxygen, and drug particles loaded onto them can avoid triggering unwanted immune reactions.
In fact, the team used what was a hurdle in previous studies to their advantage this time. The researchers had found that drug nanoparticles would often be sheared off the blood cells as they squeezed through the narrow capillaries in the lungs. That’s not helpful if you’re trying to deliver drugs to the spleen – but it’s very useful if the lungs themselves are the target.
The drug payload that the team chose was a small protein called CXCL10, which is a chemokine that attracts immune cells to a potentially dangerous invader such as cancer.
“Lung metastases deplete certain kinds of chemokines from their local environment, which means the signal that should attract beneficial white blood cells to fight the tumor is gone,” says Anvay Ukidve, co-first author of the study. “We hypothesized that providing that chemokine signal at the tumor site could help restore the body’s normal immune response and enable it to attack the tumors.”
The team designed their nanoparticles so that they would only come off in the lungs, even dotting their surfaces with an antibody that binds to a protein commonly found on cells in lung blood vessels. These nanoparticles were then loaded with the CXCL10 payload.
The researchers call the drug-loaded nanoparticles “ImmunoBait,” and when these were attached to red blood cells, they dubbed the whole system erythrocyte-anchored systemic immunotherapy (EASI).
Next, the EASI system was tested on mice, which had breast cancer that had metastasized to the lungs. The team found that the ImmunoBait particles remained in the lungs for up to six hours after EASI injection, with most of them focused around the cancer. CXCL10 levels remained high for 72 hours, which the researchers suggest was a result of the body responding by producing its own chemokines. In response, several different types of immune cells also increased in number in the lungs.
The researchers then investigated how well the treatment could slow the progression of the cancer. The team surgically removed the animals’ primary tumors, then treated different groups with either EASI, ImmunoBait nanoparticles not attached to blood cells, or CXCL10 not contained in ImmunoBait.
The full EASI system was found to work up to four times better than CXCL10 alone, and six times better than ImmunoBait alone. After 37 days, the EASI mice all had fewer than 20 metastatic nodules, compared to up to 100 for the other mice. They also lived longer – a quarter of them lived for the full 40 days of the test, while all other mice passed away in under 20 days.
The EASI treatment might also provide longer lasting protection against cancer re-emerging. In their blood the treated mice had a higher number of CD8 immune cells, which circulate for longer to keep an eye out for reappearance of a previous threat. Mice were reinjected with the same cancer cells after treatment, and those that had been treated with EASI had much lower tumor growth than untreated animals.
“These findings highlight the ability of our EASI system to convert the biological adversity of metastasis into a unique therapeutic opportunity against metastatic cancers,” says Samir Mitragotri, senior author of the study.
As promising as the results sound, the usual caveats apply. There’s no guarantee that the treatment would work in humans, and further studies will need to be done to ensure the safety and efficacy before any clinical trials could begin. Still, it’s promising.
The research was published in the journal Nature Biomedical Engineering.
Source: Harvard Wyss Institute
