The immune system is one of the great achievements of evolution. It detects and responds to viruses, bacteria, parasites, tumour cells and even attacks by inert objects. Similarly, our efforts to understand and decipher how our own immune system works is also one of humanity’s great achievements. A clear example of this is the fact that, in the last 50 years alone, vaccines have saved 154 million lives according to the World Health Organisation.

Today immunology, the branch of biomedical science that studies the immune system, is going much further. It’s redefining biomedicine, paving the way for new advances in the prevention, diagnosis and treatment of all kinds of diseases, from cancer to neurological disorders. In World Immunisation Week we explore, together with three researchers from the CaixaResearch network, how this discipline is transforming the way we approach key areas of research, and reflect on the potential of the CaixaResearch Institute as a driver of research and innovation in this field.

Training immune cells to deal with cancer

CAR-T cell therapies are one of the most promising new therapeutic approaches to cancer. This kind of therapy genetically modifies a type of immune cell present in our body, the T-lymphocytes, to recognise and destroy tumour cells more effectively and precisely. However, extracting and reprogramming T-cells from each patient entails a significant cost that, in many cases, limits this therapy’s application.

Marc Güell, CaixaResearch researcher and ICREA Research Professor at the Universitat Pompeu Fabra in Barcelona, is leading a project that seeks to use viruses as vectors to modify T-cells in the patient’s own body. The idea is that viruses reach the lymphocytes and introduce the genetic modification, making it possible to apply CAR-T therapies for cancer via a simple injection. This would greatly simplify treatments and reduce their cost.

“We’ve developed virus-like particles (VLPs) that are very precise, so they only enter T-lymphocytes and not other cells. They also manage to evade the immune system, which helps them to survive and reduces the body’s inflammatory response” explains Güell. “In addition to our work, there are also other immunological approaches against cancer that have great potential. For example, some seek to reinforce the body’s natural response to cancer by targeting proteins that normally limit the immune system’s action”.

Marc Güell, CaixaResearch researcher and ICREA Research Professor at the Universitat Pompeu Fabra in Barcelona.

Understanding the immune response to infection

Every time our body suffers an infection our immune system responds. However, it doesn’t always respond in the same way but activates a response tailored to each type of pathogen. The success of this very specific response depends largely on communication between the cells of the immune system, a process that Nuria Martínez, CaixaResearch researcher at the Centro de Biología Molecular Severo Ochoa del Consejo Superior de Investigaciones Científicas y la Universidad Autónoma de Madrid (CSIC-UAM), is trying to understand in depth.

“We know that immune cells communicate by direct contact or at a distance through a series of proteins called cytokines, but our studies suggest they may also be using molecules generated by the metabolism to exchange information, which we’ve termed metabolic communication” explains Martínez. “Understanding this language could open up new avenues for improving vaccines or treating immune diseases with nutritional interventions”.

The researcher believes that immunology is more important than ever, as advances in this biomedical field have revolutionised the way we understand, diagnose and treat infectious diseases. “Thanks to our better understanding of the immune system and its response to different pathogens, it has been possible to develop more effective vaccines, innovative immunomodulatory therapies and more precise diagnostic tools” she adds.

Nuria Martínez, CaixaResearch researcher at the Centro de Biología Molecular Severo Ochoa del Consejo Superior de Investigaciones Científicas y la Universidad Autónoma de Madrid (CSIC-UAM).

When the immune system attacks the brain

Sometimes the immune system gets confused and acts against our own body, as is the case of autoimmune encephalitis. The most common occurrence is when the immune system attacks a protein in brain cells called the NMDA receptor. This affects mostly young adults and children, causing symptoms such as behavioural changes, psychosis, memory loss, seizures, decreased consciousness and even changes in the area of the brain that controls breathing. Although treatment is available and the disease is often curable, patients can continue to experience psychiatric and cognitive disorders for months or even years.

Josep Dalmau, a researcher at Hospital Clínic-IDIBAPS and a recent addition to the CaixaResearch Institute, is working to better understand the symptoms and causes of this prolonged recovery phase of this disease by studying patients. “In parallel to studies with patients, we’ve developed an animal model of the disease that will help us to better understand the biological mechanisms, identify biomarkers and develop new treatment strategies” explains Dalmau.

“Immunology has made considerable advances in the research of neurological diseases, especially autoimmune ones,” adds the researcher. “Very effective treatments have been developed for diseases such as multiple sclerosis, and the autoimmune origin of different diseases has been discovered, such as autoimmune encephalitis, of which more than 40 types have been described. Moreover, advances in immunology have helped us better understand the mechanisms and, therefore, how to approach the treatment of processes such as cancer or infections that can trigger an immune response directed against the brain and other parts of the nervous system.”

Josep Dalmau, researcher at Hospital Clínic-IDIBAPS and a recent addition to the CaixaResearch Institute.

A pioneering centre to boost immunology research

In the coming months, the CaixaResearch Institute will open its doors in Barcelona, bringing together international researchers to study immune system processes and how they interact with the most prevalent diseases. It will therefore become Spain’s first research centre specialising in immunology and one of the first in Europe. “This is great news. I’m sure it will become a key component of the city’s biomedical ecosystem” says Marc Güell.

“Its location in a city that’s already a major player in biomedical research represents a great opportunity. For example, in the field of neuroimmunology, several centres in the city are international leaders in the study of autoimmune encephalitis, peripheral neuropathies and multiple sclerosis” explains Josep Dalmau. “The current scenario of biomedical research in immunology is unprecedented; we’re seeing advances occurring at an extraordinary rate. The vision of the CaixaResearch Institute is perfectly in line with this exceptional moment”.

“Scientific research advances thanks to the specialised work of individual groups, but above all thanks to collaboration between teams with complementary approaches” concludes Nuria Martínez. “The creation of the CaixaResearch Institute represents a strategic opportunity to promote synergies between researchers with common interests but diverse perspectives. This collaborative environment will undoubtedly accelerate advances in many different areas of immunology”.