Recently, I listened to a podcast entitled, Immunotherapy – knocking out cancer with a one-two punch. Having been affected indirectly by cancer and wanting to go into drug research in the future, I find drug discovery particularly interesting. 1 in 2 people in the UK will get cancer which is an incredibly high statistic and is the biggest killer which is why continuous research is so important. This podcast was about the new treatments that have been developed from immunotherapy research. Immunotherapy help adapt responses within the immune system which can then be used to treat a wider range of cancers and tumours, which in turn means that more patients can receive treatment. As the title says, fighting cancer with both sides of the immune system is more effective than using one then the other, “like a one-two punch in boxing.”
Cancer cells avoid immune defences such as T-cells and antibodies which allows cancer cells to continue to replicate and form tumours. Immunotherapy research has shown how cancer cells evade these cells as well as macrophages, dendritic cells and natural killer cells. Ongoing research means that new and improved methods of fighting cancer can be developed.
The first round of immunotherapies developed to treat cancer were monoclonal antibodies which are immune cells that are clones of their parent cell. These cells bind to the antigens on tumour cells e.g. HER2 on breast cancer cells which highlights the cancer cells to the other immune cells so the cancer cells can be destroyed. But this type of immunotherapy only works if the cancer displays a specific type of antigen.
The next immunotherapy developed were T-cell checkpoint inhibitors, which are a type of lymphocyte, and bind to molecules such as PD-L1 which stops immune cells from attacking non-harmful cells. This can induce long term responses in some patients with melanoma, bladder cancer and specific types of lung cancer.
The third phase of immunotherapies are in development. This round tries to use both innate immunity (non-specific defence mechanisms within the body) and adaptive immunity (antigen specific immune responses). Macrophages are at the centre of this research as it has shown that macrophages can fight cancer in two ways. Firstly, the general pattern of abnormal antigens is recognised (not specific antigens) by innate immune cells and respond to a wider range of cancer cells than adaptive immune cells and antibodies. For example, macrophages can attract and activate cells from the adaptive immune system e.g. T-cells. Healthy cells in the body express a protein – CD47 which prevents macrophages identify these healthy cells and in turn prevents phagocytosis. Diseased cells don’t express the CD47 protein which is how macrophages can identify a foreign cell within the body. Once detected, phagocytosis and other immune defence responses are triggered. However, cancer cells express CD47 which means they are harder to detect within the body – tumours can then develop. Monoclonal antibodies can block the CD47 being expressed on cancer cells and then the cancer cells are detected and attacked. Tumour targeted antibodies called rituximab can be supplied to the body which increases immune responses.
Clinical trials into these immunotherapies are ongoing but giving positive results as the toxicity of this treatment is much less than traditional methods and minor side effects are seen. In addition to this, this immunotherapy generally doesn’t attack healthy cells and is a more targeted form of treatment. Some side effects include transient anaemia but a strategy to increase the production of red blood cells has been implemented which occurs before initiating the immunotherapy treatment.
Research has also shown that this innate-adaptive immunotherapy can be applied to other diseases such as cardiovascular diseases, fibrotic diseases and infectious diseases.