Four Vall d'Hebron projects selected for the CaixaImpulse Health Innovation programme

”la Caixa” Foundation, within the CaixaImpulse Health Innovation Call 2023, has awarded a total of €3.3 millions to 29 health innovation projects. Four of these projects are led by researchers at Vall d'Hebron Campus.

CaixaImpulse Innovation helps to transfer scientific knowledge to society and encourages the creation of new products, services and companies related to life sciences. It supports innovative biomedical projects by helping them to validate their asset/s and define their valorisation and exploitation strategy, and by bringing them closer to the market.

The call is carried out in collaboration with Caixa Capital Risc, one of the leading venture capital investors in Spain, with more than twenty years of experience.

Below is a list of Vall d'Hebron projects that have been selected for this programme:

A new therapeutic approach to increase efficiency of existing cancer immunotherapies based on checkpoint inhibitors

• Leader of the project: Rodrigo Toledo, head of the Biomarkers and Clonal Dynamics Group at Vall d'Hebron Institute of Oncology (VHIO)
• Grant received: 48.700 euros

In recent years, significant progress has been made in the field of cancer immunotherapy. Immune checkpoint inhibitor-based therapies have shown benefits in the treatment of several types of tumours and, after showing exceptional improvements in some patients, have been approved for use in the fight against melanoma, kidney, bladder and lung cancer, but have also shown promising results in other tumour types. However, despite the progress made, most patients do not respond to these treatments: the overall response rate is only 20 %. There is therefore an urgent need to identify new therapeutic targets and design new drugs that can be used in combination with existing immunotherapies to enhance their therapeutic efficacy and patient outcomes.

The project will design and test the effectiveness and safety of a new drug molecule that can be combined with these immunotherapies to increase their efficacy. This molecule will target the ferroptosis pathway, a lipid oxidation process that causes cell death and can regulate the efficacy of immunotherapy. The results of the project could pave the way for a new therapeutic approach based on the combination of immunotherapy and new drugs to overcome resistance to immune checkpoint inhibitors.

New predictive biomarker for the development and progression of non-alcoholic fatty liver disease

• Leader of the project: David Martínez Selva, principal investigator of the Diabetes and Metabolism group at Vall d'Hebron Research Institute (VHIR)
• Grant received: 50.000 euros

Non-alcoholic fatty liver disease is one of the most common liver diseases in the world. It is caused by excessive fat accumulation in the liver and is exacerbated by factors like obesity and diabetes. It is known as the "silent killer disease" because its progression is very gradual and most patients with the disease do not experience symptoms and therefore remain unaware of their condition. Around 25 % of patients develop non-alcoholic steatohepatitis, characterised by liver inflammation and fibrosis, which can lead to pathologies such as liver cirrhosis or cancer. It is estimated that by 2023 this disease will become the main reason for liver transplantation globally.

There are still no approved drugs available to treat non-alcoholic fatty liver disease. One of the main reasons for this is the lack of non-invasive clinical biomarkers, which poses a significant challenge for the development of new medications. While certain molecules have been identified as potential biomarkers, biopsy remains one of the most routine diagnostic techniques. Its main disadvantages include its invasive nature and the variability of the technique. This highlights the urgent need for non-invasive biomarkers that facilitate both the diagnosis and monitoring of disease progression and the therapeutic efficacy of treatments under development.

In previous studies with an animal model, the team has identified two proteins which, when combined with a mathematical algorithm, can be used as a non-invasive biomarker to predict the onset and progression of various stages of the disease, including the most severe ones, such as steatohepatitis. The project aims to advance in the validation of this new biomarker, which could offer an alternative to liver biopsy. It will help identify individuals suffering from the disease and predict its progression, which will have important implications for improving their quality of life. It will also facilitate the development of new drugs to treat these conditions.

Validation of a new technique to detect breast cancer from breast milk

• Leader of the project: Ana Vivancos, head of the Genomics laboratory at VHIO, and Cristina Saura, head of the Breast Unit at Vall d'Hebron University Hospital and the Breast Cancer group at VHIO
• Grant received: 50.000 euros

Breast cancer that occurs during pregnancy and postpartum, the most common in women under 45 years of age, is usually diagnosed at advanced stages compared to other breast cancers, which worsens its prognosis. Postpartum breast cancer is particularly aggressive, with a higher risk of metastasis and mortality.

In previous studies the project team has shown that breast milk of breast cancer patients contains tumour-cell-derived DNA (or ctDNA). Tests conducted so far indicate that tumour variants are found in the DNA isolated from breast milk in up to 78 % of cases.

Based on that discovery, in this project the team will conduct a clinical trial involving more than 5,000 women, with the aim of incorporating this new diagnostic system into routine clinical practice. The aim is to verify the suitability of liquid biopsy in breast milk as a diagnostic test for detecting pregnancy-associated breast cancer in early stages. The clinical trial will use a test developed in the team’s laboratory based on next-generation technology, which has already been employed in the previously mentioned studies. This test must comply with the current European regulation governing in vitro diagnostic medical products, which entails a complex, rigorous validation process.

A new immunosuppressive drug to prevent organ transplant rejection

• Leader of the project: Oriol Bestard, head of the Nephrology Department at Vall d'Hebron University Hospital and co-head of the Nephrology and kidney transplantation group at VHIR
• Grant received: 148.500 euros

Organ, tissue and cell transplantation has become a global practice that can prolong and improve the quality of life for patients. Advances in harvesting, preservation, transplantation and immunosuppression techniques have improved the effectiveness of transplants. However, although the volume of organ transplants has grown exponentially over recent years, long-term transplant outcomes have not improved much in the last few decades. This is primarily due to the significant side effects of current immunosuppressive drugs, which are essential to prevent immediate transplant rejection but result in high associated morbidity and mortality.

The project team has developed a second-generation immunosuppressive molecule, structurally modified to enhance its immunomodulatory properties and effectively prevent transplant rejection by suppressing the activity of T and B cells, which are the main immune system cells responsible for causing transplant rejection. This molecule inhibits the production of antibodies against the transplanted organ by B lymphocytes, thereby improving the immunosuppressive profile of the immunosuppressants currently in use, but with the important difference that it lacks the most relevant adverse effects associated with these drugs.

In this phase, the objectives of the project are to compare the in vivo efficacy of this new immunosuppressive drug with respect to commonly used treatments in two experimental animal models, evaluate the mechanisms that prevent transplant rejection through the new molecule, conduct performance studies including the development of a stable production line for the drug and establish a pre-clinical regulatory strategy for technology transfer.