Finding new ways to boost the body's immune system for triple negative breast cancers

Triple negative breast cancer can be more aggressive and harder to treat than other types of breast cancer. This is because we don’t have targeted treatments for it, like we do for other forms of the disease.

We need better treatments for triple negative breast cancer. And John’s group hope that using the immune system will offer new treatment options.

The immune system can recognise and kill cancer cells, but cancer cells can learn to hide from it. CAR T cell therapy works by training T cells in the lab to recognise and destroy cancer cells. This therapy has transformed treatment for some blood cancers. But breast cancers can weaken or ‘switch off’ parts of the immune system, which can stop CAR T cell therapy from working properly.

John and his team have developed a new type of “armoured” CAR T cell designed specifically to overcome the harsh environment created by triple negative breast cancer. These CAR T cells don’t just target the tumour directly, they’re also built to resist the signals that cancer cells use to shut down the immune system. Now, they want to explore how effective this therapy is for hard-to-treat breast cancers.

John’s team have 2 key focusses for their research:

1. Understanding more about triple negative breast cancer that doesn’t respond to chemotherapy and current immunotherapy
   
   Triple negative breast cancer cells have clever ways to resist chemotherapy. They can also hide from the immune system, stopping immunotherapy treatments from working. There are many ways these breast cancer cells do this. 
   
   John and his team are studying signals from two important pathways called NKG2D and CXCR2. When these pathways are used by cancer cells, they can help them hide from the immune system. So by learning how these signals work in triple negative breast cancer, they hope to find ways to block them and give the immune system a better chance of fighting the breast cancer cells.  
   
   As part of this work, the team will also study circulating tumour cells found in the blood of people with triple negative breast cancer. If these cells show markers linked to the NKG2D or CXCR2 pathways, it could suggest that these pathways are important targets for new drugs. This information could then guide future clinical trials of new treatments.
   
   
2. Identifying features linked to resistance or response to treatment
   
   The researchers have developed a CAR T cell to recognise and kill cancer cells. They’ve tested this treatment in the lab and found these CAR T cells have a strong ability to kill breast cancer. Now, the team is testing this treatment in an early clinical trial with people who have advanced, hard-to-treat cancers including triple negative breast cancer.
   
   The main aim of this first study is to check whether the treatment is safe and whether the CAR T cells can find and attack cancer cells in people. The information gathered will help researchers understand how the CAR T cells behave in the body and guide the design of future trials - including those focused specifically on triple negative breast cancer.

We need better treatments for triple negative breast cancer. And harnessing the power of the immune system to kill cancer cells could be the answer. So understanding how we can better train T cells to find and kill breast cancer cells will open new doors for more effective treatments. 

Over 8000 people are diagnosed with triple negative breast cancer in the UK every year. That’s 15% of all breast cancer diagnoses.