October 4, 2022

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Immunotherapy + mRNA treat triple negative breast cancer and prevent recurrence

Immunotherapy + mRNA treat triple negative breast cancer and prevent recurrence



 

Immunotherapy + mRNA treat triple negative breast cancer and prevent recurrence. 

 

Breast cancer is the most common cancer in women, and in 2020, breast cancer replaced lung cancer and has become the world’s largest cancer , according to the latest global cancer burden datareleased by WHO International Agency for Research on Cancer (IARC) in 2020.

Globally, there were 2.26 million new cases of breast cancer and 680,000 deaths. In some countries, the incidence of breast cancer is also increasing year by year. According to the WHO forecast, there will be 410,000 new breast cancer cases in China in 2020.

 

Most breast cancers have a good prognosis, but about 15% of breast cancers are triple negative breast cancers (TNBC) , which are caused by estrogen receptor (ER) , progesterone receptor (PR) , human epidermal growth factor receptor- 2 (HER-2) deficiency is named after it.

Triple-negative breast cancer is the most aggressive breast cancer, it is more likely to spread and metastasize, and it is easy to recur. Moreover, due to the lack of therapeutic targets and limited therapeutic drugs, it has always been a difficult point in breast cancer treatment. Also known as ” the worst breast cancer “.

 

Recently, researchers from the Del Mar Institute of Medicine in Spain published a research paper entitled: LCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer in Nature Cancer.

 

This study found that cancer stem cells in triple-negative breast tumors underexpressed ligand-dependent corepressor (LCOR) , which led to their escape from immunotherapy.

On this basis, the research team used LCOR mRNA in combination with a PD-L1 inhibitor to completely eliminate triple-negative breast cancer cells in a mouse model, prevent the recurrence of cancer, and achieve a complete cure.

 

Immunotherapy + mRNA treat triple negative breast cancer and prevent recurrence

 

 

Although triple-negative breast cancer accounts for only 15% of all breast cancers, it is the fastest-growing subtype of breast cancer and affects young patients significantly.

 

Cancer stem cells (Cancer Stem Cells) are cells in tumors with self-renewal ability and can generate heterogeneous tumor cells, which play an important role in the survival, proliferation, metastasis and recurrence of cancer cells.

 

When using immunotherapy such as immune checkpoint inhibitors, cancer stem cells are able to evade immunotherapy, leading to evasion and resistance to immunotherapy. What is the mechanism behind this?

 

In this study, the research team found that cancer stem cells in triple-negative breast cancer had low expression of ligand-dependent co-suppressor factor (LCOR) , causing the immune system to be “invisible” to it, which also led to the clinical treatment of immunotherapy. Triple-negative breast cancer is less effective.

 

The research team further found that activating the expression of the LCOR gene in a mouse model reversed the immune escape of cancer stem cells and resensitized them to immunotherapy.

 

The research team validated it in clinical samples from triple-negative breast cancer patients and found that patients who responded to immune checkpoint inhibitors had higher levels of LCOR gene expression .

 

Immunotherapy + mRNA treat triple negative breast cancer and prevent recurrence

 

Inspired by the COVID-19 mRNA vaccine , the research team wants to deliver the mRNA of the LCOR gene into tumor cells in a similar way, so that the immune system can re-recognize it.

 

The research team used LCOR mRNA delivered by extracellular vesicles in combination with PD-L1 inhibitors to treat a mouse model of triple-negative breast cancer. The results showed that 49 of the 50 treated mice developed cancer.

Complete remission, the only one that did not respond was because of loss of ectopic expression of LCOR. All 49 mice in complete remission were free of tumor recurrence 2 months after drug withdrawal .

 

The research team further followed up 15 of the mice for up to 1 year. None of the mice had tumor recurrence, while the lifespan of laboratory mice was only 1-3 years, which shows that this combination therapy can eradicate and completely The tumors in these mice were cured.

 

Immunotherapy + mRNA treat triple negative breast cancer and prevent recurrence

 

Collectively, this study found and demonstrated an important role for the LCOR gene in regulating tumor immunogenicity and cancer cell response to tumor immunotherapy. In triple-negative breast cancer, the expression level of LCOR in cancer stem cells is associated with the clinical efficacy of immune checkpoint inhibitors.

The study further demonstrates that LCOR mRNA delivery via extracellular vesicles (EVs) in combination with PD-L1 inhibitors can overcome drug resistance in triple-negative breast cancer and eradicate cancer cells and prevent cancer recurrence in preclinical models.

These data support the LCOR gene as a promising target for enhancing immune checkpoint blockade therapy in triple-negative breast cancer.

 

Immunotherapy + mRNA treat triple negative breast cancer and prevent recurrence

 

It is reported that the research team has applied for a technology patent for the combined use of LCOR mRNA and immunotherapy, and will create a company to transform this technology patent and promote its clinical application.

 

 

 

 

 

 

 

Reference :
https://www.nature.com/articles/s43018-022-00339-4

Immunotherapy + mRNA treat triple negative breast cancer and prevent recurrence

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