In the world of cancer treatment, think of some types of immunotherapy as stealth weapons in which immune cells known as T-cells are taught to recognize cancer and fight malignant tumors.
But what if the T-cells run up against a wall or ring of extracellular material around the tumor that prevents them from invading?
“This is a physical phenomenon,” says Herbert Levine, Northeastern University distinguished professor of physics and bioengineering.
“Cancer tumors very often have a physical barrier surrounding the entire tumor, a sort of capsule or sheet which tries to prevent the immune cells from entering,” he says.
It’s a scenario that occurs all too often when treating many types of solid tumor cancers including but not limited to melanoma, non-small cell lung cancer and triple-negative breast cancer, he says
“Immunotherapy has been highlighted as a great accomplishment, but if you actually look at the numbers, the percentage of people, the percentage of cancer types for which it really works is still pretty limited,” Levine says.
The growing field of mechanobiology hopes to overcome treatment hurdles by partnering biologists with engineers and physicists who understand physical barriers and how they interact with cells, says Levine, who spoke at a two-day Global Summit on Mechanobiology and Mechanomedicine on Northeastern’s Boston campus.
Traditionally, medical and biology experts studying genes and mutation and causative factors such as cigarette smoking have not focused on this type of physical effect, Levine says.
Physical forces and the interactions of different cells with each other are the “sort of things physicists and engineers typically think about,” he says.
“Mechanobiology is an attempt to meld those two different ways of thinking about the problem into one.”
The idea is to “create a more global understanding of the limitations of current therapies and what some of the ways forward might be.”
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Levine’s own interest is in the tumor microenvironment, but he says mechanobiology extends beyond oncology to fields such as cardiology and regenerative medicine.
“It’s a broad undertaking. It’s not meant to be focused on a specific problem,” he says.
A biologist will try to figure out how cells encode the blueprint for treatment while the engineer wants to understand how the regrowth “physically works in the real world in real space,” he says.
Think of the engineer as being on the cellular construction site, Levine says.
“The blueprint is what should be happening, but then you have to actually make sure you have all the right construction workers to actually get it done and to make sure you’re doing it right,” he says.
With immunotherapy, Levine studies the problem of why T-cells that recognize malignant cells can’t enter them to kill them.
“It’s like they’re having a duel, but the tumor is winning,” he says. “I talk about how the building material around the tumor can be very, very dense. The immune system might not be able to make it through.”
To make matters more complicated, other cells called fibroblasts cooperate with the cancer to block T-cell access. Call them cancer helpers, Levine says.
The ultimate goal is to give the immune system a boost, such as through experimental drug treatment that prevents tumors from building strong walls in the first place, as demonstrated by researchers in a recent publication, he says.
“That’s very promising, but it was only done in one particular type of mouse model,” Levine says. “We want to understand how that occurred because we want to be able to extend that to other types of cancer.”
The National Cancer Institute helped seed the field of mechanobiology and mechanomedicine by funding a program called physical oncology about 10 years ago, Levine says.
“That program ended as a formal program, but it had many descendants. It created a lasting effect,” as have efforts by the National Science Foundation to see to what extent physics could help with the understanding of cancer.
“We were trained somewhat differently, but in terms of what we try to do it is not so different at the end of the day,” Levine says.
“If we knew all the answers, if the biology community or the bioengineering community knew all the answers, we wouldn’t have to do this. But obviously we don’t know all the answers. Even though it’s called engineering, it’s still very much at the forefront of research.”