Almost 50 years ago, in 1970, the first studies were launched that laid the foundations of immunotherapy, an innovative treatment against cancer based on making the immune system attack tumor cells. But it was not until twenty years later that the Japanese researcher Tasuku Honjo and his team discovered a mechanism to boost the natural defenses of patients for this purpose. This discovery earned Honjo the 2018 Nobel Prize in Medicine (along with the American James P. Allison) for his contribution to oncology.
What is immunotherapy and how does it work?
Cells in the human body can mutate and proliferate very quickly, becoming foreign [unrecognized] cells. The immune system works by detecting different molecules, but if there is cancer, it is blocked. By intervening in the function of a protein called PD-1, the immune system is reactivated to attack cancer cells and expel foreign elements.
What are the advantages of immunotherapy in patients?
One of them is that it has far fewer adverse effects than chemotherapy because it does not attack normal healthy cells. In addition, theoretically, it can be used to combat any type of cancer: today it is already applied to some seventeen modalities, and the number continues to increase. Another benefit is that it has a very long-lasting effect. It has been observed that when chemotherapy is given, many tumors tend to reappear, but if they are reduced or eliminated after immunotherapy, the result is usually maintained.
So, to what extent does this treatment eliminate the chances of side effects?
As I pointed out before, conventional methods – with drugs or radiation – attack all cells, without distinguishing whether they are normal or altered. But, in addition, immunotherapy does not affect the immune system, unlike previous therapies. Even so, there are risks, as in those cases in which the patient’s defenses are very strong. Then, when boosted, the immune system itself can become confused and attack itself when it detects an abnormal situation.
What aspects must be taken into account to apply immunotherapy to a patient?
Currently we do not have any optimal biomarker -indicator. The most common is to see if the tumor has mutations, which helps the body detect abnormalities. Now we must investigate new biomarkers so that immunotherapy benefits more and more patients.
And what is the key to expanding your field of action?
There are many people working on it, but the combinations between different treatments are going to be fundamental. These would include the new molecules plus another therapeutic technique, such as chemotherapy or radiotherapy.
Apart from PD-1, are there any other elements that are showing promising signs in the fight against cancer?
Other molecules and proteins are being investigated; it is a line of study with many possibilities.
How useful is the data obtained in clinical practice for further progress?
Currently there are many experiments that take this information into account, but it will still take a few years until they are finished. Then we will see what results they bring and how they can be used.
In what types of tumors has immunotherapy shown to be most effective?
The best results have been found in melanomas, but those achieved with lung cancer also stand out. One of the keys is that these two types of diseases tend to have a high number of genetic mutations.
Is it necessary to contribute more resources to R&D to continue advancing in this matter?
Yes, today research is very expensive, especially in biology. Very new and sophisticated technologies are being developed, at a very high cost, which requires increased funding and human resources.
If you look at those R&D projects, do you have any clues as to what the next steps might be in the fight against cancer?
I believe that in addition to seeking other therapeutic targets, the combination of treatments that take into account the activity of T cells – a type of lymphocyte or white blood cell that protects the body from infection – will be essential to progress in this regard. Advances in treatments against various tumors have substantially changed its prognosis.
Will there be diseases that surpass cancer in terms of mortality levels?
Currently there are neurodegenerative ailments, such as dementia or Alzheimer’s, that affect more and more elderly people and lead to other health problems. We have not been able to prevent the development of these diseases, responsible for many deaths, so perhaps research on them should be increased.
What projects are you currently working on?
I try to find out what is the molecular mechanism of the immune system, how genes change and the involvement of lymphocytes. The objective is to determine how this process can be acted upon and to find applications for clinical practice.
Interview by Nieves Sebastián
