Immunotherapies for cancer are valuable options in anti-cancer treatment.
But some cancers are more difficult to target with this strategy than others.
US scientists report a new type of immunotherapy that dramatically extends the survival of mice that have triple negative breast tumours, a difficult-to-treat form of cancer.
The researchers will present their results at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo.
It features more than 6,000 presentations on a wide range of science topics.
A 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 recognised by the immune system, that are unique to the tumour,” says Cassandra Callmann, Ph.D., who is presenting the work.
“If you don’t have a known tumour-specific antigen, it’s hard to train your immune system to go after the tumour while ignoring healthy cells.”
According to the Triple Negative Breast Cancer Foundation, this disease accounts for 15-20% of all breast cancers.
The tumour gets its name from the fact that it tests negative for the oestrogen 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 tumour-specific antigen.
“The idea was to take tumour 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 tumour 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 tumour cell lysates from stressed tumour cells into SNAs.
The researchers tested the treatment on mice in which mouse triple negative breast cancer tumours were implanted.
Two-thirds of mice receiving SNAs with oxidised lysates experienced complete tumour 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 oxidised 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 oxidising 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 oxidised and non-oxidised lysates.
The oxidised lysate/SNA approach might prove useful for treating other tumours, 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.
Source: American Chemical Society