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Harnessing the immune system to fight cancer

Cancer remains one of the biggest killers worldwide, accounting for one in six deaths according to figures from the World Health Organization. As such, discovering and honing new cancer treatments remains a major priority in the healthcare industry across the globe. Having met with success in treating specific cancers, including melanoma and leukaemia, immunotherapy has become a new pillar of the cancer treatment landscape – and a number of specialised research teams, like the one led by Melita Irving, are now exploring immunotherapy options for different tumours. We had the opportunity to speak with Melita about her work.

Simply put, immunotherapy is about developing treatments that harness a cancer patient’s immune system to fight the disease. But, as Melita Irving, Group Leader at the Ludwig Institute for Cancer Research and the University of Lausanne, explained to us, immunotherapy encompasses a wide range of possible treatments. Thus far, there has been quite a lot of research on the development of monoclonal antibodies that bind to inhibitory receptors in tumours and kickstart the immune system. For example, treating patients with anti-PD-1 or anti-PD-L1 antibodies can ‘release the brakes’ on the patient’s innate regulatory response and help naturally occurring immune cells to attack the tumour.

But a major focus for many researchers at the Ludwig Institute are T-cell therapies. T cells are a type of white blood cell that can recognise and directly kill cancer cells. T-cell therapies, then, involve taking the cells from a patient’s own immune system, expanding them under optimal conditions and then infusing them back into the patient to fight the cancer. In Melita’s research group, as she put it: ‘We go a step further, in that we genetically modify the T cells with a receptor to help them recognise and kill the patient’s specific tumour.’ Thus far, this type of treatment has shown itself to be very potent for certain types of leukaemia: what’s called chimeric antigen receptor T-cell therapy – or CAR T-cell therapy for short – has been proven, in some cases, to cure advanced haematological malignancies that didn’t respond to other treatments.

Building on this, Melita and her team are now looking to tackle solid tumours, which are a bit more complex. After all, as she reminded us, ‘cancer’ is really many different types of diseases, depending on where in the body it is located. Notably, a solid tumour differs from a liquid one, like leukaemia, for example, in that it’s made up not just of cancerous cells but a range of different cells and connective tissues: solid tumours develop a whole network of blood vessels to bring themselves nutrients and oxygen, as well as get rid of waste. What’s more, solid tumours can hijack the body’s immune cells to help them grow and thrive. The immune system features T regulatory cells, which dampen the body’s immune response so that you don’t develop autoimmunity. But when a tumour takes on these T regulatory cells, it can suppress the body’s immune response, making the cancer even more difficult to treat.

As such, Melita and her colleagues are now developing gene-engineered T cells to target these complex solid tumour systems, in combination with other classic treatments, like chemotherapy and radiation. After all, as she stated, ‘T cells are great killers, but they often need some support, especially in these very suppressive environments’. With time, the hope is that these therapies will become more and more personalised to the patient, with scientists able to tailor exactly what is targeted in the overall treatment plan to give the patient the best prognosis possible.

Of course, there are challenges to overcome. Melita was keen to stress the importance of safety mechanisms, given how potent immunotherapy treatments can be, which leads to an elevated ‘risk of toxicity’. Indeed, CAR T-cell therapies are essentially living drugs that form memory and can stay in the patient’s system for the rest of their life. On the one hand, this persistence is critical for the CAR T cells’ function, in that they continue to robustly attack and kill cancerous cells over a long period of time. But when targeting solid tumours, as she outlined, ‘you run the risk that the T cells will attack healthy tissues as well as the tumour itself, which in extreme cases can be fatal’.

In addition, there are logistical hurdles to overcome. You need advanced (and therefore expensive) infrastructure to produce these immune cells, as well as exceptionally skilled clinicians who know how to administer the therapies to patients. As a result, immunotherapy is currently restricted to a specific context: generally advanced cancer cases that fulfil specific criteria in developed countries. But Melita expressed hope that production and transportation costs would decrease as technology advances, allowing scientists to optimise their engineering tools, the design of receptors and more.

 We’ve still got work to do, but I really think this is the future of cancer research. T-cell (and other immune cell-based) therapies have such huge potential.

In this promising landscape, collaboration between industry and academia is crucial. It’s just as well, then, that the Biopôle campus is set up to foster this. As Melita recognised, if you want to see novel technologies make a real-world impact on patients, you must create bridges between bench and bedside via biopharma – and such bridges are easy to build in Biopôle’s interconnected life sciences ecosystem. In fact, Professor George Coukos, Director of the Department of Oncology at UNIL-CHUV and Director of the Lausanne branch of the Ludwig Institute for Cancer Research, works closely with various industry players, including a range of Biopôle life sciences companies.

Lausanne has become a major centre of cancer research, attracting both talent and money to its prestigious hospitals and research centres, including the CHUV, University of Lausanne, EPFL and ISREC. Melita explained how important it is that researchers can access funding from both the Swiss government and the canton of Vaud to experiment with groundbreaking techniques and technologies. The most promising of these are then rolled out to industry stakeholders, many of which maintain a presence in the Swiss Health Valley. In Melita’s estimation, ‘Lausanne is really on the map now: it’s become a hub for oncological research, bringing together people with different areas of expertise, but all sharing a common goal of developing cancer therapies.’

Moreover, Melita stressed that immunotherapy and cellular therapies are now being recognised across the world. She expressed interest in collaborating with colleagues and specialists locally and abroad, noting that ‘working with engineers, protein modellers and practitioners with different experiences and expertise is crucial to advance the field’. She was even hopeful that this would lead, in time, to a democratisation of immunotherapy: ‘Certainly, you always need to have a certain level of infrastructure to deliver treatment to patients, especially if something goes awry, but I do think these treatments will become ever more mainstream with time, benefitting countless cancer patients from a wide variety of socioeconomic and geographical contexts.’

‘There’s no comparison between a patient who can be effectively treated with one to two shots, versus one who is in and out of hospital for 10 to 15 years.

And, as she reminded us, you can’t put a price on a patient’s quality of life: ‘There’s no comparison between a patient who can be effectively treated with one to two shots, versus one who is in and out of hospital for 10 to 15 years. Not only is this more cost-effective in the long term, but it gives the patient their life back. So, there are still challenges ahead, but the future for immunotherapy is bright.’

Melita Irving
Melita Irving, Group Leader at Department of Oncology, UNIL-CHUV and Ludwig Cancer Research

Melita Irving, originally from Canada, has been working in the field of T-cell engineering for cancer immunotherapy in Lausanne since 2007. Since 2013, she has worked as a Group Leader at the Ludwig Cancer Research and the University of Lausanne.

Ludwig Cancer Research
Ludwig Cancer Research is an international community of distinguished scientists dedicated to preventing and controlling cancer. American businessman Daniel K. Ludwig began to support cancer research with the establishment of the Ludwig Institute for Cancer Research in 1971. Today, the scientific efforts endowed through his resources have grown to encompass the Ludwig Institute and the Ludwig Centers at six U.S. institutions, all pursuing breakthroughs to alter the course of cancer.
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