Dr Emma Blamont, Senior Research Officer at Breakthrough Breast Cancer, investigates whether there is a future for vaccination in breast cancer.
It’s a familiar and not very enjoyable experience. The trip to the GP’s surgery, the tense wait, your name being called, the rolling up of your sleeve, the feeling of the needle puncturing your skin. Seconds later it’s all over, and you’re on your way to being protected against an infectious disease; be it measles as a child, or typhoid as an adult on your way to a tropical holiday.
Vaccines are arguably the greatest advance in medical history, having saved more lives than any other intervention. But imagine if we could protect against cancer by receiving a vaccine. Will this ever be the case?
Our natural defence
From the moment we are born we encounter numerous microbes, some of which are disease-causing organisms called pathogens. As babies, we are protected from these pathogens and the diseases they cause by the antibodies we receive from our mother’s breast milk. Post-weaning, we become more susceptible to these infections as we depend on our own immune system, which needs to learn to recognise and mount responses to these foreign bodies, or “non-self”. This ability to distinguish self from non-self is a crucial part of our immune system and is needed to protect us from illness whilst preventing our immune systems from turning against the healthy cells in our bodies. It’s a phenomenon known as auto-immunity.
The very first time we are infected by a particular pathogen, our immune system has no way of recognising it and we are left to suffer the symptoms of the disease. Shortly after becoming infected our immune system starts fighting back, generating a disease-specific response: specialised white blood cells called B cells make large amounts of antibodies; others called killer T cells recognise and kill infected cells. These responses fight and limit the spread of infection so that a full recovery can be made as quickly as possible. After this initial response, so-called “memory cells” are made to protect against the disease should you become infected again.
Educating the immune system
Vaccines work by tricking the immune system into mounting a response to a pathogen in the absence of an infection. They are usually made from killed or weakened pathogen in the case of the polio and chicken pox vaccines, or small parts of the pathogen as is the case for the tetanus vaccine, which uses inactivated tetanus toxin.
This type of “preventive” vaccine educates our immune system to be able to recognise and respond to pathogens, protecting us from ever developing an illness.
A second type of vaccine – the therapeutic vaccine – also exists, which is designed to stimulate an immune response in a patient who already has a disease. Research in this area has piqued the interest of cancer researchers looking to find the next generation of treatments.
Harnessing the immune system to fight cancer
The idea of using the immune system to fight cancer is an old one, originating in the late 19th century through the work of American bone surgeon William Coley. He noticed that bone cancer patients who developed bacterial infections after surgery seemed to have a better outcome than those who did not.
This gave him the idea that infection stimulated the patient’s immune system, enabling it to fight off the cancer. Coley began injecting his patients with mixtures of bacteria known as Coley toxins, which were used in America until the 1950s when they were replaced by the treatments that we know today, such as chemotherapy. No research has yet provided solid evidence that Coley’s toxins are effective at treating cancer but his initial work sparked interest in a new way to treat cancer called immunotherapy.
Preventive cancer vaccines
So can we teach the immune system to specifically recognise and kill cancer cells? This is the Holy Grail of cancer immunology. Such a treatment would enable tumour cells to be targeted and would spare healthy cells – meaning that treatments would not have such severe side effects. This is no easy task since tumour cells are “self”, which the immune system has been taught to ignore.
Preventive cancer vaccines developed against cancers caused by infectious agents already exist and have been successful in reducing rates of certain cancers. The most well-known vaccines are those for cervical cancer, Gardasil and Cervarix. These vaccines generate antibody responses against two strains of the Human Papilloma Virus, HPV 16 and 18, which together cause more than 70% of cervical cancers. These vaccines are now offered to all teenage girls to protect them from becoming infected with HPV that may cause them to develop cervical cancer later in life.
Picking a vaccine target
For most cancers, including breast cancer, there is no infectious agent implicated in the causation of disease. This makes the development of a cancer vaccine a challenging prospect. How do you vaccinate against “self” whilst avoiding auto-immunity?
Several labs are now working on this problem. The key is to find a molecule present on cancer cells but not healthy cells, which is also capable of activating the immune response. These molecules can then be used to teach the immune system to recognise and attack cells with this molecule.
A recent paper published in the journal Clinical Cancer Research described the use of a molecule called mammaglobin-A as an immune target. This molecule is present on 80% of breast tumours so represents a target with a lot of potential impact. The study recruited 14 volunteers with secondary breast cancer who were “vaccinated” with mammaglobin-A. It was designed to test whether the vaccine was safe, and whether it could generate immune responses to mammaglobin A.
The vaccine turned out to be safe when administered and gave the patients few side effects. Killer T cells (the ones that attack and destroy foreign cells) were generated in response to vaccination, and importantly these cells could kill breast cancer cells when tested in the lab. The senior researcher on the study, William Gillanders, said: “Being able to target mammaglobin is exciting. In theory, this means we could treat a large number of breast cancer patients with potentially fewer side effects.”
So is there a future for vaccination in breast cancer?
This research is still at an early stage but researchers are planning a larger study in newly diagnosed breast cancer patients. If this proves to be safe and effective, then with further testing, this vaccine may eventually be available for use as a therapy.
At the moment these vaccines are being tested as treatments for people who already have cancer. But based on the success of this work, we could eventually see vaccines being used to prevent people from developing the disease in the first place. Perhaps in the future we could see our first preventive vaccine for breast cancer but we are still some distance away. To use a vaccine for prevention in healthy individuals it would need to be shown that this vaccine really does have minimal side effects and that the benefit outweighs the risks.
So who knows, perhaps in 20 years’ time, I, along with other women, could be heading to the GP for a routine vaccination for breast cancer. Let’s hope this is the case.