Cancer immunotherapy has hit the headlines over the past few days, with some outstanding successes seen in preliminary trials. But what exactly is immunotherapy, and what are its advantages over existing treatment strategies? Being an immunologist myself, this is something that I am particularly interested in and excited about. In simple terms, cancer immunotherapy is using the body’s innate immune system to attack and treat cancer, and this can be achieved in a number of different ways. I found this infographic from the Cancer Research Institute very informative and a great overview on cancer immunotherapies.
Many different types of immunotherapy are now being used and developed to treat cancer, including:
- Monoclonal Antibodies – antibodies are naturally produced by the body to recognise foreign antigens and bind to them. This antibody binding can have a number of outcomes, such as the direct killing of the cell, recruiting other cells of the immune system to eliminate the cell, or marking the cell for phagocytosis. In cancer immunotherapy, the monoclonal antibody is targeted against particular cancer cell antigens to bring about their destruction. Monoclonal antibodies are also being used for the targeted delivery of chemotherapy drugs directly to cancer cells. These so-called antibody-drug conjugates (ADCs) are composed of a monoclonal antibody specific to the cancer cell onto which are attached toxic drugs, the antibody thus delivering its toxic payload directly to the cancer cell.
- Immune Checkpoint Inhibitors – the immune system requires a mechanism to stop it attacking self antigens over foreign antigens, and this is achieved through immune checkpoints that need to be activated or inactivated to bring about an immune response. Cancerous cells have developed ways to utilise these checkpoints to turn off the immune system and avoid detection and destruction. One such checkpoint protein is PD-1. PD-1 is found on T-cells (the immune system’s assassins) and when it binds to PD-L1 on normal cells, it signals to the T-cell not to attack. Cancer cells have evolved to express large amounts of PD-L1 to prevent attack by T-cells. By using monoclonal antibodies against PD-L1 or PD-1, you can essentially keep the T-cells switched-on and active against cancer cells.
- Cancer Vaccines – these fall into two broad types: vaccines that use part of the cancer cell or cancer antigens to stimulate the immune system to recognise and destroy cancer cells, and vaccines to prevent certain viral infections that are known to promote cancer (such as the human papilloma virus).
- T-Cell Therapy – as we have seen above, T-cells are the immune system’s hit men, so approaches have been studied to better equip T-cells to recognise and eliminate cancer cells; it was this approach that hit the headlines recently with such outstanding results. In this approach the T-cell receptor (the bit that recognises the cancer cell) is genetically engineered to make it more efficient at finding and destroying cancer cells.
- Non-Specific Immunotherapy – this type of immunotherapy is not specific to cancer cells, but gives a general boost to the immune system, which can aid in the removal of cancer cells, but not exclusively. Cytokines such as Interleukin-2 (IL-2), Interleukin-21 (IL-21) and Interferon-alpha (IFN-α) fall into the category of non-specific immunotherapies.
Immunotherapy Risks and Rewards
As the recent news headlines have shown, immunotherapy offers huge rewards for the treatment of cancer. There are many reasons for this. Firstly, they are highly targeted, so you can attack just the cancer cells themselves rather than chemotherapy and radiotherapy which are non-specific, thus reducing the unpleasant side-effects from treatment. Secondly, the immune system has evolved immunological memory so that immunotherapy offers the potential for a long-lasting treatment so any reoccurrence is quickly dealt with. Finally, as a protection mechanism that the body has developed and fine-tuned over thousands of years, it is a powerful weapon aginst anything it sees as ‘foreign’, such as a cancer cell.
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However, immunotherapy does not come without risks, some of which I highlighted in a previous blog (Danger! Unexploded Antibody!). Basically, you are tampering with the body’s natural- and extremely potent- defence system, so you have to ensure that immunotherapies are fully characterised by analytical methods, including UHPLC and Mass Spectrometry, to ensure efficacy and safety. In addition, using checkpoint inhibitors and certain monoclonal antibodies can also have the side effects of making patients more prone to infections, as you risk turning down or turning off completely certain elements of the immune system.
In all, immunotherapy offers a very promising prospect for the treatment of cancer. However, there is still a lot more work to be done to prove their long-term efficacy, especially in solid tumours, and long-term safety. I do believe, though, that our amazing immune system has given us the tools and insight to make a real difference in the way we treat cancer in the future.