"Cell therapies to fight cancer have had great success in blood cancers but haven't worked well with solid tumors," said lead author Dr. Matthias Stephan, a faculty member in the Fred Hutch Clinical Research Division. "Our findings take a significant step toward making cell therapies effective against solid tumors by showing that a thin metal mesh loaded with T cells engineered to fight ovarian cancer cleared tumors in 70% of the treated mice."
Solid tumors, including cancers of the breast, ovary and pancreas, have a variety of tactics to hide from and fight back against cancer-killing immune cells like CAR (chimeric antigen receptor) T cells. Simply injecting anti-cancer cells has not worked; they don't reach the tumor or if they do reach the cancerous cells, they tire out in trying to kill them and are then shed from the body.
Stephan designs materials that are safe in the body and can carry cancer-fighting cells to tumors. "In addition to minimizing side effects in patients, our ultimate goal is to make T-cell therapies faster and cheaper to make, and easier to deliver to patients." he said.
In a step toward that goal, Stephan's latest study loaded CAR T cells targeting ovarian cancer onto a porous, mesh-like metal film and then placed the film on tumors.
"This is not just a passive delivery device," Stephan said. "It's a release platform that triggers an expansion of CAR T cells that can overcome defenses that tumors make against the immune cells."
The researchers used thin, nearly translucent metal films made by Monarch Biosciences (MonarchBio), which helped fund the project. The films are 10 micrometers thick, which is 1 millionth of a meter, or about seven times thinner than the average width of a human hair. Made of nickel titanium, the film can safely be implanted within the body and is used in other medical devices.
Viewed under a powerful microscope, the film has minuscule spaces that can be configured into different patterns. The spaces can be filled with drugs or other liquids and then implanted in the body, where the liquids ooze out and find their targets.