Nearly 50 years ago, in 1970, the first studies were launched that laid the foundation for immunotherapy, an innovative cancer treatment based on making the immune system attack tumour cells. However, it wasn’t until 20 years later that Japanese researcher, Tasuku Honjo and his team discovered a mechanism to enhance the natural defenses of patients for that 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, becoming alien cells. The immune system works by detecting different molecules, but if there are cancerous cells, the immune response is deactivates, meaning that the cells are not attacked. Intervening on the function of a protein called PD-1, it reactivates the immune system to attack cancer cells and expels foreign elements.
What are the benefits of immunotherapy?
One 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: it has already applied to 17 modalities, and the number continues to increase. Another benefit is that it has a long lasting effect. It has been observed that when chemotherapy is given, many tumours tend to come back, but if they are reduced or eliminated after immunotherapy, the result is usually maintained.
To what extent does this treatment eliminate the likelihood of side effects?
As stated earlier, conventional methods - used with drugs or radiation - attack all cells, without distinguishing whether they are normal or altered. In addition, immunotherapy does not affect the immune system, unlike previous therapies. Even so, there are risks, for example, cases where 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 should be taken into consideration when using immunotherapy on a patient?
Currently there is no optimal biomarker. The most common is to look for mutations in the tumour, which helps the body detect abnormalities. New biomarkers must be investigated so that immunotherapy can benefit more and more patients.
What is the key to broadening its scope?
There are a lot of people working on it, but the combinations between different treatments are going to be fundamental. These treatments would include new molecules plus another therapeutic technique, such as chemotherapy or radiation therapy.
Apart from PD-1, is there any other element that is 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?
There are currently many experiments that take this information into account, but it will still be a few years before they are finished. Then we will see what results they bring and how they can be used.
In what type of tumours has immunotherapy shown to be most effective?
The best results have been detected in melanomas, but also with lung cancer. One of the keys is that these two types of diseases usually register a high number of genetic mutations.
Is it necessary to provide more resources for R&D in order to make further progress in this area?
Yes, nowadays research is very expensive, especially in biology. New and sophisticated technologies are being developed, at a very high cost, and increased funding and human resources are needed.
By looking at these R&D projects, do you have any clues as to what the next steps in the fight against cancer might be?
I think in addition to looking for other therapeutic targets, combining treatments that take into account the activity of T cells - a type of lymphocyte or white blood cell that protects the body from infections - it will be fundamental to progress in this direction. Advances in treatments for the various tumors have substantially changed their prognosis.
Will there be diseases that overcome cancer in terms of mortality levels?
Neurodegenerative ailments, such as dementia or Alzheimer’s disease, are now affecting more and more elderly people and causing other health problems. We have not been able to prevent the development of these diseases, which are responsible for many deaths, and research into them should perhaps be increased.
What projects are you currently working on?
I’m trying to figure out what the molecular mechanism of the immune system is, how genes change, and the involvement of lymphocytes. The goal is to determine how this process can be acted upon and to find applications for clinical practice.