Immunotherapy – The new hope in the fight against cancer

In Germany alone, around 1.5 million people suffer from some form of cancer. Elvira was one of them. In 2005, at the age of 36, the estate agent was diagnosed with Hodgkin's disease. After undergoing chemotherapy things were initially looking good – until the cancer returned a year and a half later. That was a shock for Elvira, who found she now belonged to a group of patients for whom hitherto there had been little hope of finding a cure.

 

There was a degree of luck in the estate agent’s misfortune. She was given the opportunity to test new drugs and take part in experimental immunotherapy. The effectiveness of this form of treatment in the case of the supposedly incurable Hodgkin's disease was most recently demonstrated by a study published in 20151. According to this study, immunotherapy improves the health of 87% of patients with Hodgkin's disease and eliminates the cancer completely in 26% – as was the case with Elvira.

Given these results, some observers are talking of a revolution in cancer treatment. This may be true for Hodgkin's disease, but no generalisations can be deduced from this statement. On the contrary: treatment outcomes differ considerably depending on the type and severity of the cancer and can vary widely from patient to patient. It works for some, but in others it triggers additional and sometimes severe complications. How can such an enormous spectrum be explained and what is immunotherapy actually all about? 

Our immune system is extremely complex and works with control mechanisms, knowledge of which has until now only been rudimentary. Cells known as T cells play a dominant role. These immune-system cells can recognise and eliminate intruders such as viruses, bacteria and even cancerous cells. The T cells therefore trigger a controlled immune response. This has to be strong enough to destroy all the harmful cells without causing too much damage to the body's own healthy cells.

The activity of the T cells is controlled via immune molecules. These have either an activating (stimulatory) or blocking (inhibitory) effect on the immune cells – and exert an effect precisely at those sites where our T cells interact with cancerous cells, for example. In medicine, the sites where these interactions take place are called immune checkpoints. Each T cell has hundreds of such checkpoints and uses them to routinely investigate the molecules of other cells to verify their identity. If all immune checkpoints register endogenous, i.e. immunosuppressive molecules, the T cell remains in resting mode. It is activated, however, as soon as the first immune checkpoints identify harmful molecules – the force of the immune response increases relative to the number of immune checkpoints sounding the alarm simultaneously per T cell.

Why does this mechanism not always work and cause cancerous cells in the body to multiply? The answer to this question led to a realisation that ultimately brought about a breakthrough in immunotherapy. It was the realisation that some cancer cells disguise themselves by imitating endogenous molecules. They are not in evidence at the immune checkpoints. The T cell is not alerted and remains inactive.

Immunotherapy now uses a similar strategy – but with opposite objectives. Medical and pharmaceutical research is now able, for the first time, to develop customised antibodies using new molecular genetic methods. They are either designed in such a way that they are falsely identified by the immune checkpoints as specific tumour molecules, thereby strengthening the immune reaction, or they block certain receptors for inhibitory molecules at the immune checkpoints and thus increase the defence mechanisms of the T cells.

Even though immunotherapy is now considered a fourth pillar of cancer treatment alongside surgery, radiotherapy and chemotherapy, we are still at the beginning of a very long journey. It is true that the success achieved with Hodgkin's disease and other types of cancer, such as melanoma, has been remarkable. And patients who respond well to the new treatments – unfortunately there are also many others – need not fear any lasting side effects as is the case with conventional cancer treatments.

It is also true, however, that science cannot yet predict what type of immunotherapy is suitable for which patients, and which cancers it is actually qualified to treat. This issue, along with the efficacy and success of treatment in each individual, will be determined by molecular mechanisms that are still largely unknown. Questions concerning the therapeutic substances themselves are just as weighty: the precise effect they have on the immune system is still not properly understood. A lot of questions have yet to be answered.

Many challenges have yet to be tackled in the development of immune therapy – not only in medical science and pharmacology, but also in private life and health insurance. It is here that providers face new challenges, but also opportunities. Take costs, for example: individual immune therapies are expensive, accounting for up to 15% of the cancer treatment costs of primary health insurers. And that figure is rising. Any insurer that refuses to meet the cost of treatment because of the lack of long-term studies or authorised drugs without studying the matter closely is putting their own reputation at serious risk. At the same time, pressure to reduce costs will place a growing burden on state-run health systems and may well create new demand for insurance, depending on how healthcare is organised in that country. Meeting this new demand with suitable products – in the form of supplementary insurance for example – is both a challenge and an opportunity for private life and health insurers.

However, costs are only one aspect. The anticipated changes in mortality and morbidity are a second major aspect, as more and more cancers develop from terminal illnesses into chronic impairments. The insurance industry must monitor this positive development very closely and regularly amend and update the way in which it assesses risks and losses. This necessitates profound medical and actuarial expertise to a greater extent than previously. Only then is it possible to rapidly expand insurability and keep up to speed with medical research in the future.