Keeping cancer immunotherapy personal

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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.

dan-chen

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.


“Scientifically it’s a special time to be in the middle of discovering so much new biology. Our understanding of cancer biology has been turned on its head over the last few years.”
Daniel Chen, MD, PhD, Cancer Immunotherapy Development Franchise Head

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 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.

“We now have a good idea which patients will be responsive to cancer immunotherapy. And for them, the results can be transformative.”
Daniel Chen

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, Roche has identified a biomarker, the potential 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 potential 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 help activate the immune system, but it might not be enough. 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.

“We are moving beyond combinations of therapeutic antibodies with chemotherapies by exploring combinations of two or several cancer immunotherapy molecules to enable a strong and lasting immune response to tumours.”
William Pao, MD, PhD, Global Head Oncology Discovery and Translational Area Roche Pharma Research and Early Development

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.

Many cancer immunotherapy combinations, which pair immunotherapies with targeted, non-immunological drugs, are being tested in the clinic now. Another combination strategy looks at 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.

“These different approaches provide us with a broad range of possible combination therapies that could in the future potentially achieve durable survival for patients.”
William Pao

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 demonstrated positive responses to immunotherapies that are currently being studied.

Tags: Science