What if tiny, naturally occurring bubbles emitted by cells could be harnessed as a powerful way to treat the most lethal cancers? Scientists are trying to do that for pancreatic cancer, a largely incurable disease.
When they were discovered more than 30 years ago, these microscopic sacs—called exosomes—were thought to be nothing more than the cell’s waste products. But more recent research has revealed that they help cells communicate with one another by carrying valuable cargo—like proteins and RNA, a genetic messenger molecule—to other cells.
Present in the bloodstream and most other bodily fluids, exosomes are released and received by nearly any type of cell. When exosomes leave cells, they travel in the body and seek out recipient cells based on the instructions encoded by their payload.
Researchers think they can use this natural communication system to their advantage. Valerie LeBleu, assistant professor of cancer biology at the University of Texas MD Anderson Cancer Center, is working on genetically engineering exosomes to carry molecules that seek out pancreatic tumor cells to keep the cancer at bay.
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.
LeBleu’s team started with pancreatic cancer because it has such a poor outlook for patients and because there are no effective therapies. But she says exosomes could be similarly designed to target different types of cancer.
“This could become a type of personalized medicine,” she says. “It gives us hope for something more tailored to each cancer case, each patient progression, and each genomic landscape.”
The approach, detailed earlier this month in the journal Nature, has yet to be tried in humans. A few early-stage clinical trials were launched in the mid-2000s in Europe using exosomes to treat cancer, but the therapies showed little to no benefit. Those exosomes were not genetically modified.
Codiak BioSciences, based in Cambridge, Massachusetts, hopes to be the first to begin a clinical trial using engineered exosomes. The company has licensed the exosome technology from MD Anderson and is planning to begin clinical trials next year to try the technique against pancreatic cancer.
Codiak BioSciences CEO Doug Williams sees exosomes as an improvement over the idea of using nanoparticles to deliver drugs to different places in the body. “Our idea is to hijack that existing naturally occurring messaging system and put messages inside or on the surface of the exosomes that we want to deliver,” Williams says.
In fact, the MD Anderson team compared their engineered particles—dubbed “iExosomes”—with nanoparticles made of synthetic materials and found that the exosomes were more efficient.
Wei Zhang, a cancer biology researcher at Wake Forest Baptist Medical Center, says a major benefit of exosomes loaded with RNA is that they’re native to the human body and not toxic. So if the engineered exosomes work in people, they may have fewer side effects than traditional cancer treatments like chemotherapy and radiation.
Zhang says one of the biggest hurdles will be engineering the large quantity of exosomes that would be needed for human doses in clinical trials. LeBleu’s team used a billion exosomes for a single dose in mice.
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