In the second part of our Immunotherapy series, Rachel Leahy, Breast Cancer Now's Research Communications Officer, discusses breast cancer vaccines.
Time for new treatments
We’ve been using vaccines for well over a century to protect us from infectious diseases, leading to the eradication of the devastating small pox virus and preventing over 20 million deaths from measles between 2000 and 2015 alone.
Vaccines are designed to activate an immune response to a harmful ’intruder’, such as bacteria or a virus; this response will then be ‘remembered’ by the immune system, meaning it can mount a rapid attack if the intruder is encountered in the future. Scientists are now investigating whether the biology behind vaccines can be used to treat non-infectious diseases such as Alzheimer’s disease, diabetes, and cancer.
Taking on the tumour
Unlike traditional vaccines, which act to prevent disease, breast cancer vaccines are being developed as a treatment, targeting existing cancer cells with the aim of stopping tumour growth.
There are several different types of vaccine being developed to treat cancer, however ‘dendritic cell’ vaccines are currently the most relevant for breast cancer. Dendritic cells are part of the immune system and monitor our bodies for potentially harmful intruders. When dendritic cells encounter an intruder, they ingest it and break it down into small fragments of protein, known as ‘antigens’, which are then displayed on the surface of dendritic cells. These antigens then activate other immune cells called ‘T cells’, leading to an immune attack against any cells displaying the intruder’s antigen.
Producing a dendritic cell vaccine requires the patient to give a sample of blood, from which dendritic cells will be isolated and matured outside of the body. The dendritic cells are then exposed to specific antigens from the patient’s tumour. Once activated by these antigens, the dendritic cells are injected back into the patient, where they will circulate throughout the body and interact with T cells to stimulate a highly targeted immune response against the cancer cells.
The first task that researchers face is identifying a suitable antigen for the vaccine to target. As tumours are produced by the body, they share many similarities with healthy cells, so to prevent a damaging immune response against healthy tissues and organs, it’s vital that vaccines target the antigens found only on cancer cells.
Many breast cancer vaccines being developed target the protein HER2; although this protein is found on healthy breast cells, up to 20% of breast cancer cells contain abnormally high levels of HER2, which encourages the cancer to grow. There are several other exciting candidates for vaccine targets, including the protein MAGE-A3, which Breast Cancer Now-funded scientist, Professor Andrew Sewell, is currently studying.
A story of success...
Ductal carcinoma in situ (DCIS) is an early form of breast cancer confined to the milk ducts; around half of cases would progress to become invasive breast cancer if left untreated, however it’s not yet possible to predict which patients this will affect. This means that everyone diagnosed with DCIS will receive treatment, which for many patients may be unnecessary. A US-based study into the use of dendritic cell vaccines to treat HER2 positive DCIS has recently shown promising results in clinical trials.
The vaccine, which targeted the HER2 protein, caused few side effects and activated an immune response in over 80% of patients. The researchers behind the study are now planning more trials to further investigate the potential of this vaccine to treat DCIS.
A vaccine which targets several different tumour antigens, known as PANVAC, has also shown encouraging results in clinical trials. Secondary breast cancer patients who were given PANVAC alongside the chemotherapy drug docetaxel experienced a longer period of time before their disease progressed than those given docetaxel alone.
...and some setbacks
Unfortunately, the development of breast cancer vaccines is not always plain sailing, as shown recently when a Phase III clinical trial testing a vaccine for early-stage HER2 positive patients was terminated following disappointing results.
A common issue is that, although a vaccine may be able to activate an immune response against a specific antigen, this response may not be strong enough to overcome the tumour’s natural ability to suppress the immune system. Our previous immunotherapy blog discusses how tumours can manipulate the immune system to avoid being detected.
We also know that some of the drugs breast cancer patients receive – such as chemotherapy drugs and steroids, can suppress the immune system. A recent study has suggested that some of these treatments can make vaccines less effective. Identifying the optimum treatment regime may therefore be key to making sure that patients get the maximum benefit from vaccines alongside other therapies.
So what’s next for vaccines?
Before vaccines can become available to breast cancer patients, more research is needed to boost the immune system’s response to a tumour. Many studies, including this US-based clinical trial, are investigating whether the addition of molecules which provoke an immune response can enhance the vaccine’s ability to target the tumour.
Researchers also think that it may be beneficial to give patients both a vaccine and drugs which ‘unmask’ the tumour to the immune system. Early research using mice has shown that this combination of treatments delayed the return of a tumour for longer than in mice treated with the vaccine alone.
Although it’s clear that much more work is needed, we’re proud to be funding cutting edge research which will bring us closer to creating vaccines that can take on and conquer cancer as they have done for countless infectious diseases. Stay tuned for our third and final blog on immunotherapy, where we unravel the research surrounding CAR-T cell therapy.
Read the first part of our series, Breast Cancer Now explains... Immunotherapy, and stay tuned for our third and final blog on immunotherapy, where we will unravel the research surround CAR-T cell therapy.