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We’re beginning to treat cancer in a whole new way. Rather than killing cancer cells directly with chemo or radiotherapy, the latest treatments are designed to promote the body’s natural immune control over the disease.
So-called immunotherapy works to stimulate the body’s own immune system to destroy the cancer. It is not a new concept and was first described more than a century ago, but for the first time it is beginning to deliver long-lasting responses, which some are daring to call cures.
Behind these advances has been a more sophisticated understanding of the relationship between the immune system and cancer, particularly how the cancer is seen as a danger by the body and can disguise itself from immune attack. The most promising immunotherapies are antibody drugs, which target key switches on immune cells and fall into two main classes: checkpoint blockers such as ipilimumab and nivolumab, which remove the cancer’s ability to switch off the immune system, and immunostimulators such as anti-CD40 and anti-4-1BB, which promote active immune responses from the body.
There are several key reasons why weaponising the immune system in this way shows such promise in the fight against cancer. First, the immune system is mobile. Its ability to patrol the whole body means it is able to recognise cancer cells wherever they are. And cancer’s ability to spread is frequently the cause of recurrence following other treatments.
Second, the immune system is self-amplifying. It is able to increase its response as required to tackle large, advanced cancers. This property means that it will sometimes work better the more cancer is present, responding to a larger immune stimulation.
Third, the immune system can evolve and adapt to changes in the cancer. Cancers are genetically unstable, meaning that they can change and “escape” from conventional treatments. This situation is exactly what the immune system has evolved to cope with in its battle with pathogens. So as the tumour changes, the immune system can also change in parallel, keeping the cancer cells locked down.
Fourth, the immune system can recognise an almost limitless number of target molecules on the cancer. This ability to recognise so many targets at once makes it much more difficult for rare variant cancer cells to escape out of immune control by changing their appearance. It also broadens the types of cancer that may be susceptible to immunotherapy.
Finally, the immune system has memory. We see this with infectious diseases, with protection against a second round of infection from a particular germ. This is what provides us with life-long protection from some diseases after catching them as children or receiving vaccinations. For cancer, this means that the immune system can be “immunised” to the cancer cells and detect and delete them if they try to grow back. Most cancer treatments only work while they are being given: an immune response can last a lifetime.
These five features of immunotherapy combine to deliver major benefits, including the ability to deliver durable, perhaps life-long responses, tantamount to cures, even in advanced, previously fatal cancers.
The challenge now is to understand why some people, and some cancers, respond much better to these therapies than others and how to increase the proportion of people who experience good responses. Data reported only last month shows that combining immunotherapy treatments by giving two checkpoint-blocking antibodies at the same time extends the number of patients with effective and lasting responses. Unfortunately, it also increases the unwanted side effects from immune attack on some of the body’s normal tissues.
While the results from the recent clinical trials are incredibly promising, it is clear that we are just at the beginning of our journey to understand the immune system and harness its power to destroy cancer. We already know that the complex interplay between the genetic make-up of the tumour, the status of someone’s immune system, and the interaction between the two will sculpt the immune response in different ways.
How, then, to best boost the immune system? We recognise that large multidisciplinary teams– comprising clinicians, immunologists, molecular biologists, geneticists and others – with concentrated resources are required. In Southampton, this will coalesce around a new purpose-built Centre for Cancer Immunology, which will open in 2017 with the aim of bringing the right people together and providing cutting edge facilities.
With the development of such centres, our understanding of the immune system in health and disease will continue the rapid expansion of immunotherapy, leading to many new opportunities for treatment. Soon these will become more specific, effective and safe – leading us into a new era of cancer treatment.
About The Author
Mark Cragg, Professor of Experimental Cancer Research, University of Southampton