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.
