Immunotherapy gains ground against cancer

The IIS Aragón researcher and professor at the University of Zaragoza, Alberto Anel, explains aspects related to immunotherapy in Heraldo de Aragón

Advances made with so-called immune checkpoint inhibitors have paved the way for new cancer therapies.

Cancer immunotherapy has developed enormously in the last decade and has become one of the pillars of the treatment of this disease, along with chemotherapy and radiotherapy. The successes achieved with so-called immune checkpoint inhibitors have paved the way for many other immune-based therapies. The advances are continuous. Both basic and clinical research in this field is in full swing.

La cancer immunotherapy It consists either of activating the patient's immune system so that it kills the tumors or of using immune cells in cancer therapy that have been previously activated against specific tumors and that are subsequently infused into the patient (cell therapy). ) or also substances produced by the immune system, such as antibodies.

Although some immunotherapies, such as the use of the tuberculosis vaccine (BCG) in bladder cancer or some antibodies directed against tumors, have already been used for a long time, It was in 2010 when the field took off, due to the application of antibodies called immune checkpoint inhibitors in melanoma therapy.

This advance was based on basic research carried out by the North American researcher Jim Allison and the Japanese researcher Tasuku Honjo, who had discovered these 'control points' in the late 80s and had thoroughly characterized their function. They also developed the blocking antibodies whose clinical application was finally carried out by a pharmaceutical company, obtaining spectacular results in patients who had no possibility of treatment and whose life expectancy was no more than two months (some of them are still alive today).

For all this, these two researchers received the Nobel Prize in Physiology and Medicine in 2018. And their story once again confirms something that another Nobel Prize winner already said when they asked him if basic research or applied research was more important and he answered that There was only basic research, from which, sometimes, some application can be drawn.

What is oncoimmunology?

Oncoimmunology could also be called tumor immunology; studies how the immune system deals with the development of cancer physiologically. Once this was understood, basic science studies in this field led to successful immunotherapy tools. 

Especially important was discovering how The immune system, while trying to eliminate tumors, affects their evolution, pushing towards tumor variants that become resistant to the molecular and cellular mechanisms used by the immune system in its fight against cancer. 

The characterization of the mechanisms through which Tumors are surrounded by a particularly immunosuppressive microenvironment, which allows the tumor to easily evade the immune response. Blocking these immunosuppressive mechanisms while activating the antitumor immune response are the challenges that must be overcome.

What is the best therapeutic combination?

In recent times it has been shown that A single therapy, whether immunotherapy, chemotherapy or radiotherapy, does not usually work alone, or if it does, patients end up relapsing. To avoid this, a great effort is being made to find the best possible combinations for the more than 200 types of cancer that exist. 

The data indicate that there will not be a panacea that works for all types of cancer, but that specific combinations will be needed for each one. Lately Clinical trials based on conjugates between chemotherapeutic drugs and antibodies are being quite successful. These drugs were too toxic when used alone and produced undesirable side effects. But by conjugating them with an antibody directed against the tumor, these undesirable effects are reduced and the effect on tumors is very effective. In addition, they can be combined with other immunotherapies to obtain better results.

What are the latest advances?

National and international experts, both basic and translational researchers, as well as oncologists and clinical researchers, have shared the latest approaches in cancer immunotherapy at an international symposium held in Zaragoza. From basic science discoveries that characterize new immunosuppressive factors that appear in the microenvironment of breast tumors and that make them resistant to chemotherapy (Lorenzo Galluzzi) to new clinical trials that demonstrate the great effectiveness of the combination of two conjugates between drugs and antibodies in bladder cancers with poor prognosis (Joaquim Bellmunt). 

Likewise, the observation, currently preclinical, of the great benefit of the tuberculosis vaccine (BCG) in the ability of the immune system to reject the growth of lung tumors (Nacho Aguiló), the development of new therapies based on T lymphocytes that secrete antibodies and activate the immune system massively and specifically against tumors (Luis Álvarez-Vallina) or the new approaches to select and activate T lymphocytes infiltrated in tumors to infuse them back into the patient to kill the tumor (Azucena González). Also the latest clinical trials of new immunotherapies in melanoma (Alfonso Berrocal), lung cancer (Mariano Provencio) or breast cancer (Mafalda Oliveira).

Source: Alberto Anel (Herald of Aragon)

Image: Unify