By Jesús Sanchez Ruiz
PhD, CRIS Project Manager
Immunotherapy has now become a familiar term in any conversation about cancer therapy. In fact, it is one of the lines of research that CRIS has been supporting over a few years in different Units, based in Madrid in the University Hospital 12 de Octubre, the University Hospital La Paz and recently the University Hospital Clínico San Carlos as well as at the Institute of Cancer Research (ICR), UK.
Although it is a concept that has been discussed for many years, it wasn’t until the 2010s that this treatment was considered a real and effective alternative to prevalent treatments of cancer. It has, in recent years started a revolution. In the case of metastatic melanoma, for example, the chances of survival were quite low, but because of immunotherapy, there is now a treatment that in many cases even remits the disease. It is true that it still has important limitations, but thanks to constant research, it is slowly beginning to be used in treating other types of cancer. Taking into consideration that it is a relatively new field that requires further exploration, the possibilities it offers are very promising.
While most often people associate immunotherapy with cancer treatments, the concept is also making a name for itself in the treatment of other conditions such as allergies, autoimmune diseases or even infectious diseases (including the prevalent coronavirus). What are the connections between these conditions and why is immunotherapy useful in all of them?
The answer is that ‘immunotherapy’ is not a single treatment but refers to a concept. In a generic way, perhaps we could define it as a therapeutic strategy in which we do not directly attack the pathology itself, but we provide our immune system with the tools to combat it in a manner relevant to each pathology.
For example, when we talk about allergies, what happens is that our body is developing an exaggerated immune response against foreign substances in our environment that are typically harmless to our bodies. Allergy immunotherapy consists of helping our body to stop this increased or exaggerated immune response and return it to normal. This is similar to what happens with autoimmune diseases, conditions in which our immune system mistakenly attacks cells or organs of our body. The goal of immunotherapy is to stop this abnormal response.
In the case of cancer immunotherapies, the treatments have a completely opposite objective. Tumour cells usually turn off the cells in our immune system responsible for destroying them, such as NK cells and T lymphocytes. Cancer cells can also hide from this type of defence and thus avoid being identified. So, tumour immunotherapy is aimed at reactivating T lymphocytes, and other anti-tumour cells and helping them find and destroy cancer cells.
In the case of COVID-19, infection with the SARS-CoV-2 coronavirus causes a complex situation. Actually, immunotherapy must correct two very different situations in this infection. On the one hand, the virus could be turning off or decreasing the number of lymphocytes, the cells that should stop the infection. To compensate for this, we need immunotherapies that help increase the lymphocytes’ ability to destroy the virus. However, this requires caution because on the other hand, the infection seems to activate an exaggerated reaction of other types of immune cells, which cause very strong inflammation and could be responsible for the most serious symptoms. To control this, we need immunotherapies that reduce this acute inflammation, but without reducing the activity of the lymphocytes that have to control the infection.
We see then, that in the case of COVID-19 the picture is quite complicated.
Fortunately, the knowledge that has been acquired about the immune system in the field of cancer is giving us important clues to understand how to help our defences to reject the infection without having serious symptoms. One of the most notable examples is the case of Tocilizumab, an immunosuppressive drug normally used in the treatment of rheumatoid arthritis and multiple myeloma and prostrate cancer. In fact, it is routinely used to treat cancer patients in order to stop certain immune reactions derived from some other treatments. One of the alarm signals that some immune systems emit during COVID-19 that then causes exaggerated inflammation, is called Interleukin 6. Tocilizumab is the antibody that blocks the receiving of such alarm signals. As these signals cannot now be transmitted well, the acute inflammation decreases rapidly. This treatment is currently being employed in several clinical trials and is demonstrating good results.
Even so, there are still great unknowns in the details of the functioning of the immune system during infection with this coronavirus. Although cancer patients are known to be a population at risk, probably because of impaired defences, what happens to their immune system during COVID-19 disease is not fully understood. Clarifying this is essential, as it would give very important clues that would allow us to anticipate the appearance of serious symptoms and therefore enable us to act sooner by providing the right treatment. If we learn the molecular details of what is happening at each moment of infection, we will be able to design good therapeutic strategies that adjust to the needs of cancer patients.
For this reason, among other initiatives, CRIS is promoting a project at the San Carlos Clinical Hospital in Madrid, involving the departments of Immunology (with the direction of Dr. Silvia Sánchez Ramón) and oncology (with Dr. Alberto Ocaña and Dr. Pedro Pérez Segura). This study will thoroughly study the immune response during COVID-19 in patients with primary (birth) and secondary immunodeficiencies (with special attention to cancer patients). Initially, 115 patients will be analysed and followed up. This study will provide vital information to understand and combat coronavirus infection in cancer patients.
We are currently experiencing an unprecedented social and health crisis, but there is hope. Despite the fact that the general public is often unaware of this, behind every pill, every medicine or treatment there are years of work carried out by researchers who are committed to developing them. Research has given us all the treatments in current medicine and will provide us with all those that are yet to come, both in the case of cancer and in the case of COVID-19. Whether these therapies come sooner or later depends only on what we support. It is in our hands. It is in our interest to continue to invest in our futures by investing in medical research.