A groundbreaking study led by engineering and medical researchers at the University of Minnesota Twin Cities shows how engineered immune cells used in new cancer therapies can overcome physical barriers to allow a patient’s own immune system to fight tumors. The research could improve cancer therapies in the future for millions of people worldwide.
The research is published in Nature
Communications, a peer-reviewed, open access, scientific journal
published by Nature Research.
Instead of using chemicals or radiation, immunotherapy
is a type of cancer treatment that helps the patient’s immune system fight
cancer. T cells are a type of white blood cell that are of key importance to
the immune system. Cytotoxic T cells are like soldiers who search out and
destroy the targeted invader cells.
While there has been success in using immunotherapy
for some types of cancer in the blood or blood-producing organs, a T cell’s job
is much more difficult in solid tumors.
“The tumor is sort of like an obstacle course, and the
T cell has to run the gauntlet to reach the cancer cells,” said Paolo
Provenzano, the senior author of the study and a biomedical engineering
associate professor in the University of Minnesota College of Science and
Engineering. “These T cells get into tumors, but they just can’t move around
well, and they can’t go where they need to go before they run out of gas and
are exhausted.”
In this first-of-its-kind study, the researchers are
working to engineer the T cells and develop engineering design criteria to
mechanically optimize the cells or make them more “fit” to overcome the
barriers. If these immune cells can recognize and get to the cancer cells, then
they can destroy the tumor.
In a fibrous mass of a tumor, the stiffness of the tumor
causes immune cells to slow down about two-fold — almost like they are running
in quicksand.
“This study is our first publication where we have
identified some structural and signaling elements where we can tune these T
cells to make them more effective cancer fighters,” said Provenzano, a
researcher in the University of Minnesota Masonic Cancer Center. “Every
‘obstacle course’ within a tumor is slightly different, but there are some
similarities. After engineering these immune cells, we found that they moved
through the tumor almost twice as fast no matter what obstacles were in their
way.”
To engineer cytotoxic T cells, the authors used
advanced gene editing technologies (also called genome editing) to change the
DNA of the T cells so they are better able to overcome the tumor’s barriers.
The ultimate goal is to slow down the cancer cells and speed up the engineered
immune cells. The researchers are working to create cells that are good at
overcoming different kinds of barriers. When these cells are mixed together,
the goal is for groups of immune cells to overcome all the different types of barriers
to reach the cancer cells.
Provenzano said the next steps are to continue
studying the mechanical properties of the cells to better understand how the
immune cells and cancer cells interact. The researchers are currently studying
engineered immune cells in rodents and in the future are planning clinical
trials in humans.
While initial research has been focused on pancreatic
cancer, Provenzano said the techniques they are developing could be used on
many types of cancers.
“Using a cell engineering approach to fight cancer is
a relatively new field,” Provenzano said. “It allows for a very personalized
approach with applications for a wide array of cancers. We feel we are
expanding a new line of research to look at how our own bodies can fight cancer.
This could have a big impact in the future.”
Source: https://twin-cities.umn.edu/news-events/new-research-optimizes-bodys-own-immune-system-fight-cancer
Journal article: https://www.nature.com/articles/s41467-021-22985-5
Image credit: Provenzano Group, University of Minnesota
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