Cancer immunotherapy – redefining vaccines
Key text
This topic is sponsored by the Sir Mark Oliphant International Frontiers of Science and Technology Conference Series.
As the leading cause of death in Australia, scientists are giving cancer a shot.
 |
You will get more from this topic if you have mastered the basics of the immune system – these links will take you to an annotated list of sites with helpful background information. |
Related publication: The Science of Immunisation: Questions and Answers
Vaccines are taken for granted in developed countries; since mass immunisation was introduced in Australia in 1924, deaths from infectious diseases have now become a rare event. You may not even know what diseases like diphtheria, pertussis or smallpox are. Those dreaded jabs save around 3 million lives worldwide, every year.
Aims to address confusion created by contradictory information in the public domain. It sets out to explain the current situation in immunisation science, including where there is scientific consensus and where uncertainties exist. (Australian Academy of Science)
Traditional vaccines were developed against antigens, foreign substances (on the surface of bacteria or viruses) that our immune system reacts to. Our immune system's reaction prepares the body to fight off any future infection by the same 'germ'. Unfortunately though, this type of vaccine can only be developed for diseases that are caused by bacteria or viruses.
Less than 20 per cent of cancers are caused by viruses, so making a vaccine for many cancers is not an easy task (Box 1: Guarding against viral cancer – Gardasil®). For patients who already have cancer, current treatments include surgery, radiotherapy and/or chemotherapy, all of which have varying degrees of success and have limited room for improvement. The need for better treatment options is increasing, with cancer now the leading cause of death in Australia (28 per cent of all deaths).
Modern research into cancer vaccines stems from a radical experiment conducted over 100 years ago. In an experiment that would never be approved today, William Coley injected cancer patients with live bacteria. Amazingly, he found that some of his patients were cured. Coley didn't fully understand why his treatment worked; however, 'Coley's toxins', as they became known, showed scientists that immunisation could be used not only to prevent disease, but also to treat pre-existing disease.
But how can we possibly develop a vaccine against our own (diseased) cells? Fortunately, cancerous cells often have substances on their surface that are not present on other body cells. These antigenic substances could be used in cancer vaccines to stimulate our immune system to attack cancer cells. However, the differences between normal body cells and cancerous cells are not always obvious (Box 2: What is cancer?). Being body cells, cancer cells are good at hiding from our immune system. Research into cancer immunotherapy is aimed at helping the immune system find these hidden cells.
Homing in on cancer cells
Unlike traditional vaccines, cancer immunotherapy treats existing disease by targeting cancerous body cells. Coley's toxins are believed to have acted by generally stimulating the body's immune response. Although progressive at the time, his early version of immunotherapy was not specific to the patient's cancer cells so was not always effective. Today cancer immunotherapy has progressed to specifically target cancer cells.
Cancer immunotherapy can be broadly divided into two categories: active immunotherapy which stimulates the body's own immune response to cancer cells and passive immunotherapy which uses parts of the immune system created outside the body to fight cancer.
Tricking the body – active immunotherapy
A clear overview of the role of different cells in the immune system.
(Nobel Foundation, Sweden)
Can we trick the immune system into attacking our own diseased cells? Trials in Australia with vaccines containing antigens found on cancerous cells, have been encouraging. In a small Melbourne-based study, 19 melanoma patients were given a vaccine containing a cancer antigen combined with a substance that promotes the immune response. Two years later, 17 of the patients which were all initially at high risk of relapse were still alive.
A promising antigen that could be used in cancer vaccines is telomerase. Telomerase is an enzyme that makes cancer cells immortal and is absent from most normal cells. By finding the active parts of telomerase, researchers in Sydney have laid the foundation for developing a telomerase vaccine.
Unlike the 'one size fits all' approach of most vaccines, active immunotherapy often requires a vaccine tailored to the individual patient's cancer cells to be effective. Tailor-made vaccines are being researched in Australia using dendritic cells. These cells are like sentries that let the body know when there is an antigen present. They do this by collecting and presenting the antigen to the body's army of killer T-cells, which then recognise and attack anything with that antigen (such as a cancer cell). But dendritic cells don't always get the message through to T-cells in cancer patients. Australian research is aimed at giving dendritic cells a helping hand by culturing them outside the body with a patient's cancer
cell antigen.
When used as a vaccine, these dendritic cells have resulted in complete remission in 15 per cent of melanoma patients.
Although they produce an immune response, being individually tailored for each patient, active immunotherapies can be expensive and time consuming. Another Australian trial is aimed at removing the need to treat dendritic cells outside the body. The vaccine Lipovaxin, combines cancer cell antigen with a substance that targets dendritic cells inside the body. Once it has combined with dendritic cells, they then present the antigen to T-cells which attack the cancer.
Despite promising results with active immunotherapy trials, vaccines tailored to a patient's cancer cell antigen can become less effective with time. This is because the antigen from any remaining cancer cells can change through mutation; vaccines have to then be redeveloped to target the changed antigen.
Magic bullets – passive immunotherapy
A graphic showing how monoclonal antibodies are produced using mouse cells.
(Access Excellence, USA)
The guided missiles of medicine, monoclonal antibodies are antibodies that are created in the laboratory to home in on and destroy cancer cells. They are created to target a specific antigen in or on cancer cells, and can be made more lethal by being loaded with toxins, chemotherapy drugs or radioactive material. Monoclonal antibodies are produced by injecting mice with antigen; the B-cells produced in response by the mice are then fused with cancer cells. This makes the B-cells immortal allowing scientists to culture these specific antibody-producing cells indefinitely. The antibodies they produce are all identical and home in on the original cancer antigen.
Monoclonal antibodies, or mAbs as they have become affectionately known, are used to treat a range of cancers. Herceptin® is a mAb that has been used successfully to treat breast cancer in Australia. It works by binding to and inactivating a protein (HER2) on the surface of cells that causes some types of breast cancer.
But mAbs aren't always the magic bullet we were promised when they were first discovered. Treatment can be expensive, needs to be repeated and has caused problems when patients' immune systems reject the foreign mouse-produced antibody. Genetic engineering to produce humanised versions (including Herceptin) have made mAbs a more attractive treatment option.
Vaccines are no longer a simple injection of inactive bacteria or viruses to prevent disease. Scientists are constantly finding new ways to train the immune system to target already diseased cells. Immunotherapy is redefining our understanding of vaccines.
Boxes
1. Guarding against viral cancer – Gardasil®
2. What is cancer?
Related Academy material
The Science of Immunisation: Questions and Answers
This publication aims to address confusion created by contradictory
information in the public domain. It sets out to explain the current
situation in immunisation science, including where there is scientific consensus and where uncertainties exist. The Science of Immunisation: Questions and Answers was prepared by a Working Group and Oversight Committee made up of
Academy Fellows and other Australian scientists with internationally
recognised expertise in immunology.
Nova - science in the news
Immunisation – protecting our children from disease
Kissing the Epstein-Barr virus goodbye?
Sun and skin – a dangerous combination
Epigenetics – beyond genes
Interviews with Australian Scientists
Professor Frank Fenner (Microbiology and virology)
Professor Ian Frazer (Immunology)
Professor Gordon Ada (Microbiology)
Sir Gustav Nossal (Immunology)
External sites are not endorsed by the Australian Academy of Science.
Posted September 2008.