Immunotherapy extends survival in mouse model of hard-to-treat breast
cancer

Date:
August 17, 2020
Source:
American Chemical Society
Summary:
Immunotherapies for cancer -- treatments that prime the immune
system to attack tumors -- are valuable weapons in the anti-cancer
arsenal. But some cancers are more difficult to target with this
strategy than others.

Today, scientists report a new immunotherapy that dramatically
extends the survival of mice that have triple negative breast
tumors, a difficult-to-treat form of cancer.



FULL STORY ========================================================================== Immunotherapies for cancer -- treatments that prime the immune system to
attack tumors -- are valuable weapons in the anti-cancer arsenal. But
some cancers are more difficult to target with this strategy than
others. Today, scientists report a new type of immunotherapy that
dramatically extends the survival of mice that have triple negative
breast tumors, a difficult-to-treat form of cancer.


==========================================================================
The researchers will present their results at the American Chemical
Society (ACS) Fall 2020 Virtual Meeting & Expo.

A brand-new video on the research is available at
http://www.acs.org/fall2020- breast-cancer.

"From an immunotherapy standpoint, one of the biggest problems with triple negative breast cancer is that it doesn't produce any known antigens, or molecules recognized by the immune system, that are unique to the tumor,"
says Cassandra Callmann, Ph.D., who is presenting the work. "If you don't
have a known tumor-specific antigen, it's hard to train your immune system
to go after the tumor while ignoring healthy cells." According to the
Triple Negative Breast Cancer Foundation, this disease accounts for 15-20%
of all breast cancers. The tumor gets its name from the fact that it tests negative for the estrogen receptor, the progesterone receptor and excess
HER2 protein -- three proteins commonly produced in large amounts by
other types of breast cancer. Because triple negative breast cancer lacks
these markers, many commonly used breast cancer drugs aren't effective.

This is one reason triple negative breast cancer has a poorer prognosis
than other forms of the disease, according to the American Cancer Society.

To develop a new type of treatment, Callmann, a postdoctoral fellow in
the lab of Chad Mirkin, Ph.D., at Northwestern University, needed to
take a different approach from conventional immunotherapies that target a tumor-specific antigen. "The idea was to take tumor cells, chop them up,
feed them to the immune system and let it figure out what to go after on
its own," Callmann says. Other researchers have tried this approach for different cancers, but they typically administer both the chopped-up tumor cells (called a lysate) and a molecule that stimulates the immune system,
known as an adjuvant, as a mixture. Instead, the team packaged the lysate
and the adjuvant together in a single nanoparticle. The nanoparticle,
called a spherical nucleic acid (SNA), contained the lysate inside
its core and many copies of a DNA adjuvant radiating from its lipid
membrane shell.

When the team injected SNAs under the skin of mice, the SNAs traveled
to the lymph nodes. There, SNAs entered the cells, released their cargo
and stimulated the cells to mount an immune response against antigens
in the lysate.

Interestingly, a stronger immune response occurred when the researchers incorporated oxidized tumor cell lysates from stressed tumor cells
into SNAs.

The researchers tested the treatment on mice in which mouse triple
negative breast cancer tumors were implanted. Two-thirds of mice receiving
SNAs with oxidized lysates experienced complete tumor remission for at
least 90 days, whereas all untreated animals died by day 30. None of
the treated mice had obvious side effects or autoimmune responses.

The therapy is not yet ready for clinical trials, Callmann says. One
of the next steps will be to investigate why the oxidized lysates work
better than regular lysates. The team has begun to identify subsets of the lysates that are more immunogenic than others. She notes that a stressed
cell could be producing different proteins, or perhaps the oxidizing
agent is changing chemical groups on proteins. To get a clearer picture, Callmann plans to conduct a proteomic analysis to identify proteins that
differ between oxidized and non-oxidized lysates.

The oxidized lysate/SNA approach might prove useful for treating other
tumors, as well. "We have demonstrated that the overall structural
presentation of a cancer vaccine or immunotherapeutic, as opposed to
simply the identity of the active chemical components, dictates its
potency, and this finding is opening doors in the field," Mirkin says.


========================================================================== Story Source: Materials provided by American_Chemical_Society. Note:
Content may be edited for style and length.


==========================================================================


Link to news story: https://www.sciencedaily.com/releases/2020/08/200817104327.htm

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