Immunotherapies will transform cancer treatment, predicts immunologist Luis Álvarez-Vallina, from the 12 de Octubre hospital and the National Cancer Research Center (CNIO) in Madrid, who yesterday received the Fero-Dr Scholarship. Baselga for an ambitious scientific project aimed at improving this type of therapies. If the drugs that have arrived in recent years have opened the way to making cancer chronic in many patients, “with immunotherapies we will finally be able to talk about curing it, something that was unthinkable,” declares Álvarez-Vallina.
Where are we now in cancer immunotherapies?
At a very exciting point. In the last ten years, immunotherapies have demonstrated therapeutic effects. CAR-T cell therapies have arrived in hematological cancers. In solid tumors we have immunotherapy drugs. The problem is that these drugs are only effective in 20-30% of cases. There is a large group of patients who need new immunotherapies.
How can immunotherapies improve with the project funded by the Fero Foundation?
We intend to develop a cell therapy strategy like the one that works in hematological cancers such as leukemias and lymphomas and transfer it to solid tumors.
“We want to transfer the strategy that works in leukemias and lymphomas to solid tumors.”
Why doesn’t it still work in solid tumors?
There are several reasons. Solid tumors are organized structures that develop defenses, making them more difficult to attack. They have an immunosuppressive environment that hinders the action of the immune system. And they are also more heterogeneous, with a greater diversity of tumor cells.
How do you hope to overcome these obstacles?
With a cellular therapy in which we will modify T cells so that they are capable of acting on various targets of the tumor, both inside the cells and on the outer membrane. With a multitarget strategy, we hope to prevent the tumor from escaping the immune system.
What are T cells?
They are key cells of the adaptive immune system [la parte del sistema inmune que reacciona ante elementos nuevos, como virus o células de cáncer]. They are responsible for monitoring what happens in cells, both on the surface and inside. And they are responsible for cellular immunity that allows the destruction of tumor cells. T cells are the basis of the immunotherapy strategy we are developing, which we have called SMART-T.
“In classical oncology it was unthinkable that advanced cancer could be cured”
What is the difference between this strategy and what immunotherapy drugs do?
Immunotherapy drugs counteract the brakes that the tumor acquires to stop the immune system. By removing these brakes, the immune system regains its ability to recognize and destroy the tumor. With these drugs, we rescue the response of the immune system. The strategy we pursue is different. It is not about rescuing the immune system but about redirecting it against the tumor. We establish a bridge between the immune system and cancer so that T cells can reach the tumor.
Where will they get the T cells for this new immunotherapy?
From the patients themselves. The idea is to extract T cells, which circulate in the bloodstream, from a blood sample. We will also carry out a study of each patient’s tumor to identify the specific targets against which the T cells should be directed. From there, we will modify the patient’s T cells so that they recognize these targets and so that they have a better ability to penetrate tumors. . We will grow them to obtain a sufficient quantity for the treatment. Finally, we will administer them to patients. It will be a personalized treatment, tailored for each case.
For what types of tumor do you think this strategy may be more effective?
In our project we will focus on lung cancer and breast cancer. But it is a strategy that could be useful for any type of solid tumor.
How long will it take to produce CAR-T cells for each patient?
Not much. The entire process can take approximately eight days.
Many patients have responded long-term and have probably already been cured.”
Some people who have received CAR-T cell immunotherapies have experienced adverse effects. Are you worried about security?
It is something that we hope to control by acting against specific intracellular targets of each tumor. We would have the toxicity problem if we acted against tumor targets that are also found in healthy tissues.
The Fero Foundation finances translational research projects, with the perspective that they reach patients. If so, when do you estimate that the SMART-T immunotherapy strategy can reach the clinic?
We are now in the preclinical phase of the project. The Fero Foundation’s funding is for two years. In this period we hope to demonstrate the effectiveness and safety of the strategy in preclinical models. [ratones]. With these results, we will be in a position to begin the regulatory process to carry out a clinical trial in patients within a period of between two and three years. One of the advantages of cell therapies is that translation to patients can be rapid.
Looking ahead, how do you foresee immunotherapies changing cancer treatment in the next five to ten years?
What is coming is impressive. RNA vaccines, bispecific antibodies, immunostimulatory treatments, combinations of different types of immunotherapy… We will have technologies that will allow us to better understand the characteristics of each patient, personalize therapies and obtain response rates much higher than those we have today. The proportion of patients who respond to immunotherapies will increase. That is precisely the objective of our project. But personalized treatments will pose a problem.
What a problem?
How to ensure that these treatments reach all the people they can benefit.
Is the fact that so many different immunotherapy strategies are being investigated a sign that we still don’t know which ones are best?
I think it is rather an example of the extraordinary complexity of the interaction between cancer and the immune system. Before we had a monolithic view of cancer. Cancer was defined by its organ of origin, as if all cancers of the same organ were equivalent. We now know that each patient has a unique disease. Every cancer and every patient is different, and we will have to personalize immunotherapy strategies to make them as effective as possible.
The immune system is capable of curing infections. Can it also cure cancer if activated with the appropriate immunotherapies?
I am convincent that is yes. We have many patients who have responded to treatment and in whom the response is long-term. Many of them have probably already been cured. This was difficult to imagine in the context of traditional oncology, where for years there was a lot of skepticism towards immunotherapies and it was unthinkable that advanced cancer could be cured. That skepticism has disappeared and I am sure that many cancers can be cured.
Gala in Barcelona
The Fero Foundation brings together 800 people
About eight hundred people attended last night the charity dinner of the Fero oncology research foundation that took place in the Drassanes Reials building in Barcelona. During the gala, the four new scientific projects financed by the foundation were announced, which represent a contribution of 540,000 euros to cancer research.
The Dr. Baselga Scholarship, created in honor of the oncologist Josep Baselga, founder of the Fero Foundation who died three years ago, has been awarded to Luis Alvarez-Vallina, from the 12 de Octubre hospital and the National Cancer Research Center in Madrid. Endowed with 300,000 euros, the scholarship will finance a research project that has the potential to transform immunotherapy treatments for solid tumors.
The other three projects will receive 80,000 euros each. The Fero-Mango Breast Cancer Project, financed by Mango and reaching its sixth edition, has been awarded to Sara Sdelci, from the Center for Genomic Regulation (CRG) in Barcelona. His research aims to improve the treatment of so-called triple negative breast cancers. Francisco Barrigafrom the Vall d’Hebron Institute of Oncology (VHIO), has received a Fero scholarship sponsored by the Ramón Areces Foundation for research aimed at improving the treatment of ovarian cancer.
For its part, Silvia Affòfrom the Idibaps institute at the Hospital Clínic in Barcelona, has received another Fero grant funded by the Bosch Aymerich Foundation for a project that will study the influence of the tumor microenvironment on bile duct cancer therapy.
The Fero Foundation gala was attended by, among other personalities, its president Silvia Garriga; the businesswoman and vice president of the foundation Sol Daurella; Marisa Falco, Countess of Godó; the bankers Josep Oliu and Manel Cerqueda; businessmen Isak Andic and José Creuheras; and the doctors Josep Tabernero, Josep M. Campistol and Jaume Padros.