A new study 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.
From:
University of Minnesota
May 14, 2021 -- 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."
https://www.sciencedaily.com/releases/2021/05/210514134222.htm
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