Body’s Own Intracellular Messengers Could Carry a Cancer Kill Switch to Tumors
By engineering exosomes’ payloads, researchers have halted pancreatic cancer in mice.
A diagnosis of pancreatic cancer usually isn’t a good one. Difficult to detect and quick to spread, the mortality rate for its most common form is a grim 93% after five years.
Which is why a team of researchers chose it as a testbed for their latest experimental treatment—one that involves using our body’s own intracellular messengers to precisely deliver a deadly payload.
The messengers, known as exosomes, are tiny packages that our cells produce and load up with proteins and RNA before releasing them into the bloodstream. There, they wind their way though the body until they reach their intended target. By adding an engineered strand of RNA to the payload, Valerie LeBleu, an assistant professor of cancer biology at the University of Texas MD Anderson Cancer Center, and her colleagues think they can halt even the most recalcitrant of tumors like late-stage pancreatic cancers.
Here’s Emily Mullin, reporting for Technology Review:
Her team extracted exosomes from human foreskin cells and modified them so that they would contain certain kinds of RNA that can turn off specific genes. They engineered the exosomes to target a gene called KRAS, which is commonly linked to pancreatic cancer. When mutated, the KRAS gene acts like an on-off switch that gets stuck in the “on” position, causing cancer cells to divide and grow.
Researchers loaded the RNA into exosomes, which they then injected into mice with pancreatic cancer. The engineered exosomes were taken up by pancreatic cells with mutated KRAS. Once inside the cancer cells, the exosomes were able to switch off the gene in mice, stopping tumor growth and extending the animals’ life spans.
In that way, exosomes behave similarly to nanoparticles, which can be loaded with cancer-fighting treatments and guided to tumor sites. But they have a leg up on synthetic nanoparticles in that they are made of cell membranes, meaning they are less likely to be rejected by a patient’s body.
The treatment isn’t limited to pancreatic cancers, though LeBleu selected that disease given its intractable nature. Given the engineered nature of the treatment, it’s possible that it can be tailored to particular patients and tumors. Plus, since they can be programmed to seek out certain cell types, the side effects would likely be significantly less than those of other treatments.
The trick, though, will be scaling it up to meet the demand. In LeBleu and her team’s trials, just one dose contained 1 billion exosomes.
Photo credit: NIH
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