Keeping cancer immunotherapy personal
Fighting cancer using patients’ own immune system is a concept that has been around for a long time, and real advances in our understanding about how to do this have been made over the last 10-15 years. We now appreciate just how many different factors affect how the immune system works, either by slowing it down or increasing its intensity. We have also learned how tumours make use of these controls for their own purposes and can basically evade an attack from the immune system.
At the Roche Group, we have a long-standing commitment to science-driven discovery in the fields of both medicine and personalised healthcare. A major element of personalised healthcare is fitting the right treatment(s) to the right patient. Humans are complex organisms and not everybody responds to a particular drug in the same way, so having a technique to predict in advance which patients are most likely to respond to therapy is a major step in how we approach treatment going forward.
One way to do this is by identifying a biomarker, a specific protein or other molecule on or within a cell that indicates whether or not a cancer is using a specific pathway to evade immune attack that we can target with a drug.
Having an identified biomarker is in some situations like the difference between shooting an arrow at a target in the dark or in the light – in the dark hitting the target can be a bit of a lottery.
The exciting aspect to this approach is that every tumour may have a potential biomarker. However, some biomarkers have proven to be more elusive than others and many have remained stubbornly hidden, though it’s not through a lack of searching! In cancer immunotherapy, the Roche Group has been successful in identifying a promising biomarker, the usefulness of which we are currently studying in pivotal trials.
Cancer immunotherapy in combination: the 1-2 punch
Even though we have identified a potential biomarker and created a promising cancer immunotherapy agent we recognise that the job is far from complete. We have to look beyond the here and now and consider the additional parts of the personalised therapy jigsaw, by looking at combinations. Because the immune system is so tightly regulated, an individual drug may achieve a necessary step toward the task of activating the immune system that by itself, however, is not sufficient. By combining two or more drugs that act in a complementary fashion, one stands a better chance of generating the kind of immune response needed to fight different tumour types, and by tailoring the combinations we should be able to treat people more effectively.
Using this approach, the first thing we need to examine is how targeted agents or chemotherapies interact with the immune system. Not all of them are bad, yet not all of them are good. Some therapies are not compatible as a combination option because they effectively disable the immune system while patients are on treatment. Other therapies, for reasons we are only now just starting to understand, actually help the immune system do its job.
Combinations have been the mainstay of cancer therapy since almost the very beginning and we have become much more sophisticated with their use, knowing how and when to use them and in which combinations. This is why we strongly believe that combination treatments will remain an essential part of cancer therapy, even with the rise of immunotherapy.
Cancer immunotherapy combinations of the future will start by pairing immunotherapies with targeted, non-immunological drugs. Many of these combinations are being tested in the clinic now and are showing signs of promising results. The next wave of combinations will probably be pairing immunotherapy doublets together with a standard of care therapy. This idea is based on understanding a particular person’s own ‘immune signature’. Knowing how an individual’s immune system will respond to immunotherapy means we can work out which aspects of the immune system need to be either accelerated and which aspects we need to slow or put the brakes on.
As long as we continue to be able to identify those people who have the right ‘immune signature’ there will be an important place for monotherapy immunotherapies, while those lacking such signatures may respond best to combinations. We are already seeing this with a subset of patients that have responded well to the immunotherapies that are currently being studied.
Is there a future for cancer vaccines?
Cancer vaccines, regarded by some as a controversial subject, are particularly important when discussing future strategies with cancer immunotherapy treatments. The history of therapeutic cancer vaccines to date has certainly been disappointing, even to the most ardent believers. However, the reason we feel this may be an important avenue of further study is that we have a greater understanding of the science than we did previously, providing an appreciation for what features of immunity have been successfully activated by vaccination and what features are lacking that prevents a successful clinical outcome.
A key new feature is our ability to identify immune biomarkers that indicate when a vaccine is needed and when it is effective. We now know that while the failures of vaccines in the past may have been clinical failures, they were not always necessarily biological failures. The ability of vaccines to initiate an immune response where one is lacking may be a perfect fit for combining with other currently studied and future cancer immunotherapies. These vaccines may help an immune response and allow the immune system to take control. For this reason we believe that vaccines may yet prove to be an extremely valuable weapon in our combination armoury.