Radical Method Uses Cells to Fight Brain Tumors
This Behind the Scenes article was provided to Live Science in partnership with the National Science Foundation.
The American Brain Tumor Association says this year nearly 70,000 people in the United States will be diagnosed with tumors that form in blood vessels, cranial nerves, lymphatic tissue and other parts of the brain. Of those, nearly 12,000 people will be diagnosed with a particularly deadly form of brain cancer called glioblastoma multiforme (GBM).
GBMs hide behind a protective barrier in the brain and, among other things, attack white blood cells that serve as the body's defense. With some innovative science, National Science Foundation- (NSF) funded researchers are working to improve the ability of those same white blood cells to attack the cancers right back.
Stefan Bossmann and Deryl Troyer at Kansas State University in Manhattan, Kan., are developing a new materials treatment method that uses a type of white blood cell called a neutrophil to slip medications past the brain's protective barrier and strike down malignant tumors directly.
"The goal of our research is to use cells as transport ships for anticancer drugs," explains Bossmann. "Defensive cells — essentially, white blood cells — have the ability of moving through [the blood-brain barrier], including bone tissue, to tumors and metastases."
In principle, using cells to carry drugs to intended targets is a pretty straightforward concept. However, creating a "cargo hold" within the cells that is sturdy enough to successfully carry a medicinal payload to a desired endpoint has been a challenge.
Previous efforts have resulted in cargo holds that leak, burst prematurely or fuse with the cells that carry them, causing the drugs to be released before reaching their target and killing the transport cells, not the tumors.
A new class of "cages"
To solve the problem, Bossmann and Troyer are developing a new type of caged liposome. Liposomes essentially are artificial bubbles created within cells that can be used as vessels to carry and administer therapeutic drugs. [Microbubbles Smuggle Drugs Transdermally]
The researchers are creating self-assembling"cages" that wrap around liposomes — turning them into more secure cargo-holds. Their process involves loading caged liposomes with anticancer medicine before up-take by neutrophils that will self-destruct and release the drugs when they reach tumors.
The PPCLs proposed by the researchers are designed to be more stable than classic liposomes, prevent systemic leaking during transport and activate only once they integrate into tumors. This should facilitate the killing of fast growing tumor cells and slow-growing cancer stem cells responsible for the reappearance of tumors and the formation of metastases that spread tumors to other parts of the body.
The proposed cell therapy method would work by taking whole blood from cancer patients, then loading redesigned cargo holds within the whole blood's neutrophils with anticancer drugs and afterwards re-injecting the modified neutrophils into the patient's blood stream.
If successful, the approach could deliver more than 50 percent of a prescribed anticancer drug dosage to a target, while leaving the patient's immune system intact. Traditional chemotherapy delivers only about 1-2 percent of a therapeutic drug dose, while nanotherapy delivers only about 10 percent.
"If they can actually do that and deliver the amount of drugs that they think they can, it could make a difference," says Mark Dewhirst, director of Duke University's Tumor Microcirculation Laboratory in Durham, N.C., "a big difference." Dewhirst, who has published more than 400 peer-reviewed articles, book chapters and reviews, is one of a number of interested observers.
A new standard of care
The project, "Neutrophil Delivery of Apoptosis-Inducing Anticancer Drugs," is one of 40 projects funded in the first round of an NSF initiative thataddresses extremely complicated and pressing scientific problems. Called INSPIRE, the initiative funds potentially transformative research that does not fit neatly into any one, scientific field, but crosses disciplinary boundaries.
"The focus of this INSPIRE project is to develop basic scientific knowledge of the materials that are being studied," says Joseph Akkara, director of the Biomaterials program in MPS. "In a larger sense, biomedical applications are at present supported by the National Institutes of Health."
NSF's Biomaterials program in its Directorate for Mathematical and Physical Sciences (MPS) funds the research. It is also co-funded by NSF's Biophotonics program along with its Materials Surface Engineering program, both in the Directorate for Engineering.
"More than half of the patients with GBM will die within a year, and more than 90 percent within three years," says the Director of NSF's Biophotonics program Leon Esterowitz. "The results from this project will exploit patient-specific, tumor-homing cells for treatment delivery and could lead to a new standard of care for brain cancers."
If successful, the strategy could expand to targeting other cell types. The researchers believe the method's principles could evolve into targeted therapies for viral, bacterial and protozoal infections. However, they acknowledge there is still a ways to go.
"Brain tumors remain a disease for which there are many challenges because of the eloquence of the site where they are," says Henry Friedman, an internationally recognized neuro-oncologist and deputy director of Duke's Preston Robert Tisch Brain Tumor Center. "No one therapy is going to be the magic bullet, but the more different interventions we have, the more likely we're going to be successful."
This new treatment method "is not going to be the only intervention necessary, but it certainly is going to be part of the spectrum of different therapies that we use," he says. "It is going to be one of additional weapons that may find a place in the treatment of malignant brain tumors."
Editor's Note: The researchers depicted in Behind the Scenes articles have been supported by the National Science Foundation, the federal agency charged with funding basic research and education across all fields of science and engineering. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the National Science Foundation. See the Behind the Scenes Archive.
