Author: Burcu Anil Kirmizitas, Edited by: Luiz Guidi
If you have seen the latest Cancer Research UK television ad campaign you may have noticed that, at the end of each ad an eerie sentence pops up on the screen: “1 in 2 people will get cancer in the UK”. Such high numbers are similar for the rest of the developed world. Because of this, efforts to understand cancer and find cures for its numerous different types are at an all time high these days. For instance, the National Cancer Research Institute reports that just between 2002 and 2009, the annual funding they provided for cancer research doubled from £257 million to around £500 million.
The therapeutic methods researchers have developed to fight cancer over the last few decades are quite versatile, ranging from ‘classics’ such as chemotherapy and radiotherapy, to the up-and-coming methods of the 21st century: hormone therapy, gene therapy and immunotherapy. What all of these methods have in common is that their aim is to treat cancer effectively. Where they differ is their side effects and the end results when it comes to efficiency. Cancer immunotherapy stands out of all these methods because it uses the body’s natural defence mechanism and brings the possibility of higher effectiveness and lower side effects.
Immunotherapy means utilising the immune system to target disease. Our immune system is the natural defender and fighter of our bodies and it attacks anything that it recognises as a biological enemy. It does this by looking for substances that are foreign to our system, and once detected, destroying them.
In the case of cancer immunotherapy, the clever thing that scientists have been doing is to use the very properties of the immune system to attack cancer cells. But how? The definition of cancer is basically that your own cells turn rogue on you. They are still cells in your body but they have their own agenda, multiplying endlessly and attacking you. But if the immune system is programmed to attack foreign molecules, how can it attack cancer cells, which are your own cells in the first place?
There are many ways through which we use the properties of the immune system as cancer therapies these days. We make vaccines and antibodies for cancer so the immune system can be prompted to recognise cancer cells as foreign. There are also inhibitors to stop the immune system from not attacking cancer cells, also known as ‘checkpoint inhibitors’. We can also take the molecules from the immune system itself and engineer them to boost the immune system’s response to cancer.
The road that has led to the current state with cancer immunotherapy has been a bumpy one, as it is the case with any new method being developed - these things are not a breeze through the park. For instance, the average percentage of patients whose cancer shrinks or disappears after treatment with approved immunotherapy drugs is on the range of 30% for melanomas and 20-25% for all cancers. Whilst these numbers are very low, it is important to remember the simple fact that there are response rates to report with these therapies in the first place, as previous therapies did not work at all on the types of cancer in question.
Part of the low response rate problem comes from the clearance of vaccines, antibodies, etc. from the blood. Our liver and our kidneys clear any medicine we take from the blood stream but how long this will take depends on the molecular nature of the medicine. The binding affinity of immunotherapy drugs to their targets is lower than conventional drugs, which leads to them spending more time circulating in the blood than at their target cells.
There are thankfully several methods to help with this issue. Take nanoparticles, for instance. They are used as cargo carriers to deliver drugs to where they are needed and protect them from the factors outside so they don’t get degraded or cleared from the blood. Scientists have recently started combining nanoparticle technology with immunotherapy to make immuno-nanomedicines.
The potential of immunotherapy, the promising results we have from the studies conducted, and the number of approved drugs have sparked the interest of private investors to the field. One interesting example was featured in Business Insider UK in April 2016: Sean Parker, the co-founder of Napster and previous Facebook president, invested $250 million in cancer immunotherapy. Another example is the $540 million that the trust fund of late businessman Daniel Ludwig awarded to six U.S. institutes in 2014 to be used in cancer immunotherapy research.
Government investment in immunotherapy and related areas, such as personalised or precision medicine, have been substantial as well. In the USA, early in 2016, the Obama administration proposed the ‘Cancer Moonshot’ initiative for $1 billion, which was included in the 21st Century Cures Act that was signed into a law by the president in December. This act alone secured $4.8 billion research funding. In the UK, the government’s latest £816 million investment in healthcare research announced in September 2016 includes immunotherapy, as did the previous rounds.
There are also various start-up and spin-off companies in the UK focusing on immunotherapy. Some of the latest ones are Achilles Therapeutics and Autolus, both University College London spin-offs, founded in 2016 and 2015 respectively. Others, which are now leading the cancer immunotherapy in the UK, include Immunocore, Adaptimmune and Oxford Biomedica in Oxford and Scancell in Nottingham.
The forecast for immunotherapy would be partially cloudy with a few showers. According to The American Association for Cancer Research, we can expect more basic science research in 2017 on immune-signaling pathways and on new biomarkers to report on immunotherapy response. On the FDA front, we are looking at more approvals of checkpoint inhibitors. As for new treatments, we will see more personalised treatments with vaccines and combinations of checkpoint inhibitors.
Cancer is not a disease that can be tackled with a cure-all method. There is an immense number of factors that can cause it. So scientists are, as always, focusing intently on the discovery of molecules, mutations and causes that are specific to certain cancers so they can be targeted by specific therapies. Immunotherapy relies heavily on such new discoveries as any other therapy but with the recent developments in research, it will definitely lead to advances we have not dreamed of before when it comes to cancer.