CLOSE
iStock
iStock

New Therapy Shrinks Five Types of Pediatric Cancers in Mice

iStock
iStock

Cancerous pediatric brain tumors are some of the most aggressive cancers to affect children, and are frequently fatal. They’re difficult to treat due to their proximity to sensitive brain tissue in tiny brains, and children’s bodies can rarely tolerate the side effects of the levels of chemotherapy and radiation necessary to shrink tumors.

But recently, researchers at Stanford Medicine, the Lucile Packard Children’s Hospital, and several other institutions successfully tested a promising immunotherapy treatment that shrank multiple tumor types in mouse models. Immunotherapy treatments harness the body’s own immune system to fight the cancer, and usually come with few to no side effects compared to chemotherapy drugs and radiation.

The collaborative study, published in Science Translational Medicine, showed results on the five most common types of pediatric tumors: Group 3 medulloblastomas (MB), atypical teratoid rhabdoid tumors (ATRT), primitive neuroectodermal tumors (PNET), pediatric glioblastoma (PG), and diffuse intrinsic pontine glioma (DIPG).

The Stanford researchers designed their study after the recent discovery of a molecule known as CD47, a protein expressed on the surface of all cells. CD47 sends a “don’t eat me” signal to the immune system’s macrophages—white blood cells whose job it is to destroy abnormal cells. “Think of the macrophages as the Pac-Man of the immune system,” Samuel Cheshier, lead study author and assistant professor of neurosurgery at Stanford Medicine, tells mental_floss.

Cancer cells have adapted to express high amounts of CD47, essentially fooling the immune system into not destroying their cells, which allows tumors to flourish. Cheshier and his team theorized that if they could block the CD47 signals on cancer cells, the macrophages would identify the cells on the cancerous tumors and eat them—without any toxicity to healthy cells. To do so, they used an antibody known as anti-CD47, which, as its name implies, blocks CD47 on the cancer from binding to a receptor on the macrophage called SIRP-alpha.

“It is this binding that tells the macrophage, 'Don't eat the tumor,'” he says. The anti-CD47 fits perfectly into the binding pocket where CD47 and SIRP-alpha interact, “like a jigsaw puzzle,” helping the macrophage correctly identify the tumor as something to be removed. “Anti-CD47 is the big power pill in Pac-Man that makes him able to eat the ghosts,” says Cheshier.

Even better, not only does anti-CD47 block the “don’t eat me” signal, it has the rare ability to pass the blood brain barrier, making it “very effective against all brain tumor types,” Cheshier says.

His team tested anti-CD47 on each of the five tumor types both in vitro (in live tissue cultured in a dish) and in vivo (human cancer cells implanted inside living mice). For the initial in vitro studies, Cheshier explains, they developed the cancer cells “in a way that preserves the cancer stem cells and allows them to grow.” Then the researchers introduced macrophages and added anti-CD47. Excitingly, the scientists “watched the macrophages eat the tumors,” he says.

Next, for each of the five tumor types, they isolated two separate lines of cancer cells taken from separate patients and cultured all 10 in the lab. Then they injected each of these different lines of tumor cells directly into the brains of 10 to 20 mice, so that a minimum of 20 animals per tumor type were tested. The tumor cells had been modified with firefly luciferase genes, making the tumors light up under scans so the scientists could track the cells’ progress. “Once we confirmed the tumor was growing, we gave some mice anti-CD47,” Cheshier says, while the control mice received none. “Only the mice that received anti-CD47 lived,” he explains.

Additionally, the scientists created an experiment where they also injected healthy human brain stem cells into mouse brains, in addition to tumor cells, and then treated some of the mice with anti-CD47. “In the mice that received anti-CD47, the normal brain cells grew normally. So there was no effect on [the healthy cells] even in the context of very active tumor killing.” Cheshier finds this result exciting because “this is the first time in any study where anyone put normal human cells with the cancer and then showed that anti-CD47 wasn’t toxic in an animal.”

Depending on the tumor type, and the amount of anti-CD47 injected, the tumors visibly shrank over the course of one week to six months—even disappearing altogether in some cases. While not every tumor was completely eliminated, Cheshier says this is most likely a matter of the length of the experiment and the amount of anti-CD47 given. “We could achieve [elimination] in every tumor type,” he says.

Of course, Cheshier warns that humans might react differently than mice, but these initial results are promising: He is most excited that a single therapy worked in all five tumor types. “You can imagine a situation where instead of giving different types of drugs for different tumors, we can just say, ‘Here is the treatment. It’s universal.’”

The pre-clinical study took four years to complete, and now the therapy has moved to phase one of a human clinical trial process, in order to test for toxicity. He has plans for phase two, which will ask the question, “Does it actually work in treating the tumor [in humans]?” Cheshier says. And phase three will be the randomized, double-blind clinical trial that hopefully proves anti-CD47 will be superior to current treatments. Meanwhile, other studies will look at its combined effects with other cancer treatments.

While there’s much further work to be done, Cheshier is very optimistic that this therapy will be both “more effective and less toxic than current standards of care. I think anti-CD47 will be part of an armamentarium where we’re using the immune system to treat cancer instead of toxic chemicals and radiation beams.”

nextArticle.image_alt|e
Emery Smith
arrow
Stones, Bones, and Wrecks
The 'Alien' Mummy Is of Course Human—And Yet, Still Unusual
Emery Smith
Emery Smith

Ata has never been an alien, but she's always been an enigma. Discovered in 2003 in a leather pouch near an abandoned mining town in Chile's Atacama Desert, the tiny, 6-inch mummy's unusual features—including a narrow, sloped head, angled eyes, missing ribs, and oddly dense bones—had both the “It's aliens!” crowd and paleopathologists intrigued. Now, a team of researchers from Stanford University School of Medicine and UC-San Francisco has completed a deep genomic analysis that reveals why Ata looks as she does.

As they lay out in a paper published this week in Genome Research, the researchers found a host of genetic mutations that doomed the fetus—some of which have never been seen before.

Stanford professor of microbiology and immunology Garry Nolan first analyzed Ata back in 2012; the mummy had been purchased by a Spanish businessman and studied by a doctor named Steven Greer, who made her a star of his UFO/ET conspiracy movie Sirius. Nolan was also given a sample of her bone marrow; his DNA analysis confirmed she was, of course, human. But Nolan's study, published in the journal Science, also found something very odd: Though she was just 6 inches long when she died—a typical size for a midterm fetus—her bones appeared to be 6 to 8 years old. This did not lead Nolan to hypothesize an alien origin for Ata, but to infer that she may have had a rare bone disorder.

The current analysis confirmed that interpretation. The researchers found 40 mutations in several genes that govern bone development; these mutations have been linked to "diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia)," they write. The latter is commonly known as dwarfism. Some of these mutations are linked to conditions including Ehlers-Danlos syndrome, which affects connective tissue, and Kabuki syndrome, which causes a range of physical deformities and cognitive issues. Other mutations known to cause disease had never before been associated with bone growth or developmental disorders until being discovered in Ata.

scientist measures the the 6-inch-long mummy called Ata, which is not an alien
Emery Smith

"Given the size of the specimen and the severity of the mutations … it seems likely the specimen was a pre-term birth," they write. "While we can only speculate as to the cause for multiple mutations in Ata's genome, the specimen was found in La Noria, one of the Atacama Desert's many abandoned nitrate mining towns, which suggests a possible role for prenatal nitrate exposure leading to DNA damage."

Though the researchers haven't identified the exact age of Ata's remains, they're estimated to be less than 500 years old (and potentially as young as 40 years old). Genomic analysis also confirms that Ata is very much not only an Earthling, but a local; her DNA is a nearest match to three individuals from the Chilote people of Chile.

In a press statement, study co-lead Atul Butte, director of the Institute for Computational Health Sciences at UC-San Francisco, stressed the potential applications of the study to genetic disorders. "For me, what really came of this study was the idea that we shouldn't stop investigating when we find one gene that might explain a symptom. It could be multiple things going wrong, and it's worth getting a full explanation, especially as we head closer and closer to gene therapy," Butte said. "We could presumably one day fix some of these disorders."

nextArticle.image_alt|e
iStock
arrow
Health
Just Two Cans of Soda a Day May Double Your Risk of Death From Heart Disease
iStock
iStock

If you've been stocking your refrigerator full of carbonated corn syrup in anticipation of warmer weather, the American Heart Association has some bad news. The advocacy group on Wednesday released results of research that demonstrate a link between consumption of sugary drinks—including soda, fruit juices, and other sweetened beverages—and an increased risk of dying from heart disease.

Study participants who reported consuming 24 ounces or more of sugary drinks per day had twice the risk of death from coronary artery disease of those who averaged less than 1 ounce daily. There was also an increased risk of death overall, including from other cardiovascular conditions.

The study, led by Emory University professor Jean Welsh, examined data taken from a longitudinal study of 17,930 adults over the age of 45 with no previous history of heart disease, stroke, or diabetes. Researchers followed participants for six years, and examined death records to determine causes. They observed a greater risk of death associated with sugary drinks even when they controlled for other factors, including race, income, education, smoking habits, and physical activity. The study does not show cause and effect, the researchers said, but does illuminate a trend.

The study also noted that while it showed an increased risk of death from heart disease, consumption of sugary foods was not shown to carry similar risk. One possible explanation is that the body metabolizes the sugars differently: Solid foods carry other nutrients, like fat and protein, that slow metabolism, while sugary drinks provide an undiluted influx of carbohydrates that the body must process.

The news will likely prove troublesome for the beverage industry, which has long contended with concerns that sugary drinks contribute to type 2 diabetes and tooth decay. Some cities, including Seattle, have introduced controversial "soda tax" plans that raise the sales tax on the drinks in an effort to discourage consumption.

SECTIONS

arrow
LIVE SMARTER
More from mental floss studios