Ultrasound remotely triggers immune cells to attack tumors in mice
without toxic side effects
Date:
August 12, 2021
Source:
University of California - San Diego
Summary:
A new cancer immunotherapy pairs ultrasound with specially
engineered CAR T cells to destroy malignant tumors while sparing
normal tissue. The new experimental therapy significantly slowed
down the growth of solid cancerous tumors in mice.
FULL STORY ========================================================================== Bioengineers at the University of California San Diego have developed
a cancer immunotherapy that pairs ultrasound with cancer-killing immune
cells to destroy malignant tumors while sparing normal tissue.
==========================================================================
The new experimental therapy significantly slowed down the growth of
solid cancerous tumors in mice.
The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed
their work in a paper published Aug. 12 inNature Biomedical Engineering.
The work addresses a longstanding problem in the field of cancer
immunotherapy: how to make chimeric antigen receptor (CAR) T-cell therapy
safe and effective at treating solid tumors.
CAR T-cell therapy is a promising new approach to treat cancer. It
involves collecting a patient's T cells and genetically engineering
them to express special receptors, called CAR, on their surface that
recognize specific antigens on cancer cells. The resulting CAR T cells
are then infused back into the patient to find and attack cells that
have the cancer antigens on their surface.
This therapy has worked well for the treatment of some blood cancers
and lymphoma, but not against solid tumors. That's because many of the
target antigens on these tumors are also expressed on normal tissues
and organs. This can cause toxic side effects that can kills cells --
these effects are known as on-target, off-tumor toxicity.
==========================================================================
"CAR T cells are so potent that they may also attack normal tissues that
are expressing the target antigens at low levels," said first author
Yiqian (Shirley) Wu, a project scientist in Wang's lab.
"The problem with standard CAR T cells is that they are always on --
they are always expressing the CAR protein, so you cannot control their activation," explained Wu.
To combat this issue, the team took standard CAR T cells and re-engineered
them so that they only express the CAR protein when ultrasound energy
is applied.
This allowed the researchers to choose where and when the genes of CAR
T cells get switched on.
"We use ultrasound to successfully control CAR T cells directly in
vivo for cancer immunotherapy," said Wang, who is a faculty member
of the Institute of Engineering in Medicine and the Center for Nano-ImmunoEngineering, both at UC San Diego. What's exciting about
the use of ultrasound, noted Wang, is that it can penetrate tens of
centimeters beneath the skin, so this type of therapy has the potential
to non-invasively treat tumors that are buried deep inside the body.
The team's approach involves injecting the re-engineered CAR T cells
into tumors in mice and then placing a small ultrasound transducer on
an area of the skin that's on top of the tumor to activate the CAR T
cells. The transducer uses what's called focused ultrasound beams to
focus or concentrate short pulses of ultrasound energy at the tumor. This causes the tumor to heat up moderately -- in this case, to a temperature
of 43 degrees Celsius (109 degrees Fahrenheit) -- without affecting the surrounding tissue. The CAR T cells in this study are equipped with
a gene that produces the CAR protein only when exposed to heat. As a
result, the CAR T cells only switch on where ultrasound is applied.
The researchers put their CAR T cells to the test against standard CAR
T cells.
In mice that were treated with the new CAR T cells, only the tumors that
were exposed to ultrasound were attacked, while other tissues in the body
were left alone. But in mice that were treated with the standard CAR T
cells, all tumors and tissue expressing the target antigen were attacked.
"This shows our CAR T-cell therapy is not only effective, but also safer,"
said Wu. "It has minimal on-target, off-tumor side effects." The work is
still in the early stages. The team will be performing more preclinical
tests and toxicity studies before it can reach clinical trials.
========================================================================== Story Source: Materials provided by
University_of_California_-_San_Diego. Original written by Liezel
Labios. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Yiqian Wu, Yahan Liu, Ziliang Huang, Xin Wang, Zhen Jin, Jiayi Li,
Praopim Limsakul, Linshan Zhu, Molly Allen, Yijia Pan, Robert
Bussell, Aaron Jacobson, Thomas Liu, Shu Chien, Yingxiao
Wang. Control of the activity of CAR-T cells within tumours via
focused ultrasound. Nature Biomedical Engineering, 2021; DOI:
10.1038/s41551-021-00779-w ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2021/08/210812123112.htm
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