CaixaResearch Advanced Oncology Research Program (2020-2025) FERO Foundation Institutional Advanced Molecular Diagnostics Program (DIAMAV) BBVA Foundation Comprehensive Program of Cancer Immunotherapy and Immunology (CAIMI II) VHIO-CRIS Program for Precision Oncology and Digitalization
CaixaResearch Advanced Oncology Research Program (2020-2025)

”la Caixa” Foundation: advancing research to drive precision therapeutics

The ongoing CaixaResearch Advanced Oncology Research Program (2020–2025) is supported by funding received from the ”la Caixa” Foundation. This institutional partnership has been instrumental in advancing VHIO's development of potent and targeted cancer therapies, strengthening existing research lines, initiating innovative projects, and taking a leading role in cutting-edge research in precision oncology.

At the helm of this program is the Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch. Directed by Elena Garralda, this unit represents a hub of transformative research, focusing on unraveling the complexity of clinical resistance mechanisms to anticancer therapies. In 2024, the unit participated in 266 phase I clinical trials, 24 of which were basket studies. Supported by a multidisciplinary team, the unit continued to expand its portfolio of phase I and basket trials, enrolling 624 patients. This year, UITM opened 90 new studies, treated over 1,314 patients throughout the year, and performed over 740 first visits.

As outlined in last year’s report, the UNIQUE CaixaResearch platform (UNderstanding cancer through sIngle cell seQUEncing) was established as a transversal initiative within our CaixaResearch Advanced Oncology Research Program, aimed at enabling next-generation single-cell sequencing. In 2024, the UNIQUE platform continued to expand its capabilities and enhance operational capabilities. While still in its early phase, important steps have been taken to maximize future impact. Two calls for specialist positions successfully closed, incorporating an expert in Single Cell Transcriptomics—now leading the HTU-Single Cell laboratory—as well as a microscopy specialist heading the HTU-Microscopy lab. The first user experiments are now underway.

A total of 22 VHIO – CaixaResearch Scientific Seminars were held, bringing together a diverse and international lineup of leading experts in oncology and biomedical research. Speakers hailed from top research institutions, covering a wide range of cutting-edge topics—from liquid biopsy and radiomics to cancer metabolism, AI in imaging, and tumor microenvironment research. These seminars continue to enrich VHIO’s scientific community.

VHIO Academy launched five international calls, all aligned with the center’s strategic focus on attracting top-tier talent. Among these, the INPhINIT ”la Caixa” Fellowship programs (Incoming & Retaining), funded by the ”la Caixa” Foundation, stand out as key initiatives to support and retain promising young researchers through competitive funding opportunities.

Innovation Support from ”la Caixa” Foundation

Innovation at VHIO is strongly supported through strategic programs from the ”la Caixa” Foundation. One of the key initiatives is driven by the CaixaResearch Institute, which contributes annually to VHIO through supporting the hiring of dedicated management personnel with expertise on innovation that have joined VHIO's specialized Innovation Unit.

In addition, the establishment of the Innovation Hub working group—bringing together CRACs (CaixaResearch Associated Centres)—has created a collaborative platform where innovation best practices are shared. This initiative provides specific training sessions tailored to researchers and innovation managers, enhancing internal technology transfer capacity and fostering a culture of innovation across institutions.

A critical challenge in innovation management within research centers is the lack of proof-of-concept funding. This funding is essential for conducting key experiments that inform the prioritization or de-prioritization of early-stage research. It plays a pivotal role in advancing projects to a higher level of maturity, making them eligible for more substantial valorization programs. In 2024, VHIO successfully secured three such proof-of-concept (PoC) projects, representing a significant step forward in overcoming this early-stage funding gap.

Building on projects already in the process of valorization—led by the Innovation Unit and supported through proof-of-concept (PoC) funding—”la Caixa” Foundation has continued to advance VHIO’s innovation efforts by providing both financial resources and expert mentoring. Notably, programs such as CaixaImpulse offer unique, specialized support in entrepreneurship and innovation training. This condensed training program is proving to be critical for VHIO personnel, particularly postdoctoral researchers.

In 2024, VHIO achieved a significant milestone with the awarding of a CaixaImpulse Consolidate (Phase II) project to Marcos Malumbres. This project had previously benefited from a PoC grant provided by the Innovation Hub in 2023, exemplifying the successful progression made possible through this integrated support system. Additionally, VHIO currently has two active CaixaImpulse Explore (Phase I) from the 2023 call, led by Ana Vivancos and Rodrigo Toledo. These projects further demonstrate the robust innovation pipeline fostered by the comprehensive and strategic support of the ”la Caixa” Foundation.

FERO Foundation Institutional Advanced Molecular DiagnosticS Program (DIAMAV)

FERO Foundation: driving advanced molecular diagnostics against cancer

Our Molecular Prescreening Program is supported by one of our Institutional Supporters and Patrons, the Fundación FERO. FERO’s Institutional Advanced Molecular Diagnostics Program (DIAMAV) catalyzes precision medicine at VHIO. Over the last decade, this program has facilitated access to advanced molecular diagnostics to more than 10,000 cancer patients and is critical in matching targeted therapeutic approaches with hundreds of clinical trial opportunities.

This pioneering program, also counting on the support and expertise provided through our Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, is co-led by VHIO’s Ana Vivancos, Paolo Nuciforo, Elena Garralda, and Rodrigo Dienstmann, Principal Investigators of our Cancer Genomics, Molecular Oncology, Early Clinical Drug Development, and Oncology Data Science – OdysSey Groups, respectively, and coordinated by Susana Aguilar Head of the VHIOTECA Unit.

Our expert team specializes on the clinical implementation of advanced molecular diagnostics to optimize therapy selection for patients being considered for enrolment in clinical trials. We also provide continued medical education on emerging cancer biomarkers to support precision cancer therapy. By advancing molecular profiling, we help match personalized treatment strategies to the unique genomic or pathologic features of each individual patient. Our researchers and clinical investigators identify specific molecular risk factors to predict the potential efficacy of targeted therapies for individual tumors. These insights support our multidisciplinary teams in assessing and determining patients eligibility for early phase clinical trials conducted at VHIO’s UTIM – CaixaResearch.

In the last trimester of 2023, we launched a monthly Molecular Tumor Board (MTB). During these meetings we discuss the results of somatic next-generation sequencing (NGS) panels and other relevant biomarkers within the clinicopathological context of individual patients. Each case discussion is supported by a focused literature review to aid in the interpretation of molecular alterations and assess their actionability for targeted therapies. Two patient cases are presented and discussed at each MTB session.

Thanks to the support from FERO, our Molecular Prescreening Program has strengthened its position as a reference in oncogenomics across Europe. Leveraging our cutting-edge technologies and platforms, we continue are extending the reach of precision cancer medicine to an increasing number of patients.

In 2024, molecular profiling studies were performed in 2,128 patients with various cancer types. This number nearly doubles the number of patients profiled annually over the past decade, averaging 1,100.

Since 2023, we have implemented the VHIO360 panel, our liquid biopsy technology developed in partnership with Guardant Health, that allows tumor molecular profiling from blood samples. Remarkably, in 2024 alone, more than 1,300 patients received this test routinely. Initially used when tissue samples were insufficient, the VHIO360 panel is now also applied to monitor the emergence of driver alterations associated with disease progression.

To further expand our capabilities, the Genomics Laboratory replaced the Nanostring panel with RNA sequencing. This new method, implemented as the Epsilon test in late 2023 and adopted as our reference RNA-based assay in 2024, enhances the detection of gene fusions and RNA expression levels. These improvements are crucial for identifying increasingly actionable cancer biomarkers, many of which are rare (affecting less than 2% of patients), such as gene fusions. Additionally, in 2024, we launched the development of a digital pathology biorepository of Molecular Prescreening images. This resource will enable the integration of imaging data with genomic, transcriptomic, and proteomic data to support advanced biomarker discovery.

FERO’s Institutional Program is instrumental in driving these advances, allowing us to bring powerful molecular technologies to more patients, accelerate research into less invasive cancer monitoring via liquid biopsy, and pioneer new diagnostics for earlier cancer detection.

BBVA Foundation Comprehensive Program of Cancer Immunotherapy and Immunology (CAIMI-II)

BBVA Foundation: generating new insights into the mechanisms of resistance and response to immune-based therapies

The Comprehensive Program of Cancer Immunotherapy and Immunology (CAIMI II) aims to advance immuno-oncology (IO) and develop novel cancer immunotherapies. With generous support from the BBVA Foundation, VHIO teams are deepening the understanding of immunological mechanisms and driving the development of safe, scalable IO-based treatments. Their efforts include identifying resistance mechanisms to immunotherapies and exploring innovative approaches such as tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies. Through CAIMI II, VHIO is emerging as a European leader in translational cancer immunotherapy research, particularly in early-phase clinical drug development.

In 2024, VHIO awarded the BBVA Foundation Innovative Research Grant, enabling researchers to explore pioneering concepts with clinical potential. This year’s grant supports Joan Seoane’s project, “Developing Novel Antibody-Based Adjuvants to Enhance Glioblastoma Immunotherapy.”

Alena Gros’ team has established a cutting-edge single-cell RNA, TCR, and cell surface protein sequencing pipeline to study tumor-specific T-cell responses. Laura Soucek’s team is enhancing immunotherapy by combining Omomyc, a MYC-inhibiting drug, with immune-stimulating agents. In preclinical lung cancer models, this combination significantly reduced tumor size and extended survival. The team is now testing higher doses and analyzing immune responses to refine this strategy for KRAS-mutant lung cancer.

VHIO’s Advanced Therapies Program continues to develop immune cell-based treatments for patients who do not respond to standard therapies. Alena Gros’ team is optimizing TIL therapy using novel immune-cytokine compounds that enhance both TIL expansion and tumor-fighting capacity. One compound promotes TIL growth, while another increases T cell specificity in ovarian tumors—potentially advancing personalized cell therapy. They are also pioneering a minimally invasive method to detect cancer-specific immune cells by analysing cell-free DNA (cfDNA) in blood samples. In collaboration with Rodrigo Toledo, this approach could reduce the need for biopsies and improve real-time tumor monitoring, especially in advanced cancers.

In parallel, Alena Gros’ team is engineering T cell receptors (TCRs) to target cancer-specific mutations. Promising TCR candidates recognize mutations in genes like PIK3CA and TP53, common in breast and cervical cancers. Their goal is to generate patient-derived, genetically modified T cells for personalized therapies.

Joaquín Arribas’ team has developed a next-generation CAR T cell therapy targeting HER2-overexpressing cancers with high precision. Their approach combines p95HER2 CAR T cells with a bispecific T cell engager (TECH2Me), enhancing tumor targeting while minimizing toxicity. By fine-tuning TECH2Me’s affinity, they ensure selective killing of cancer cells while sparing healthy tissues. In experimental experimental systems, these engineered T cells effectively eliminated HER2-positive tumors with minimal side effects. In patient-derived models, the therapy led to complete tumor regression in several cases, showing promise for treating breast, esophageal, and gastric cancers.

VHIO teams have also optimized TIL therapy—approved by the FDA in 2024—by developing less invasive immune cell extraction methods and selecting TILs that specifically target tumor mutations. They are refining preclinical models and applying high-throughput gene analysis to further enhance these therapies. Several clinical trials, including NEXTGEN-TIL, TILTS-001, and PragmaTIL, are currently evaluating safety, efficacy, and toxicity, with new studies testing TILs in combination with innovative therapies.

The VHIO Academy is rolling out educational initiatives supported by CAIMI II, including undergraduate and master’s fellowships focused on cancer immunotherapy research. The Academy has also launched international secondment fellowships for clinical residents and PhD researchers to train at leading cancer research centres. Additionally, VHIO continues to foster long-term talent through the BBVA MD-PhD program, which supports pioneering projects in immune oncology.

VHIO-CRIS Program for Precision Oncology and Digitalization

The VHIO-CRIS Program for Precision Oncology and Digitalization is driving advancements in personalized cancer medicine by supporting both biomedical and clinical research, with cancer patients as the ultimate beneficiaries of all research activities led by VHIO. This program addresses key challenges arising from the rapid expansion of research groups, the introduction of breakthrough technologies, and the overwhelming generation of big data.

This new Institutional Program funded by the CRIS contra el Cáncer Foundation, focuses on establishing and supporting new units dedicated to multimodal data digitalization and Oncology Data Science —including the Data Engineering for Research Unit, Oncology Data Science (ODysSey) Group, Bioinformatics Unit, and Biostatistics Unit. Key initiatives include developing digital platforms for analyzing, integrating, and visualizing multimodal oncology data, and creating AI-driven tools and models to integrate and visualize medical imaging alongside other cancer research data (genomic, imaging, clinical, and more) generated at VHIO. Through this Program, we aim to apply these technologies to research use cases that drive advancements in our understanding of cancer while enhancing user trust—particularly among medical oncologists and biomedical researchers—by improving the explainability of AI models. Additionally, the program seeks to empower patients and stakeholders by raising awareness of the role of patient data in research and fostering engagement with patient representatives and advocacy groups.

Major highlights in 2024:

  • Over the past year, the new Biostatistics Unit has supported 15 clinical trials and contributed to 16 Q1 publications, while advancing biomarker validation, applying complex statistical methodologies, and engaging in national and European projects focused on innovative trial designs to enhance VHIO’s oncology research.
  • The Data Engineering for Research Unit (DERU) has established robust data infrastructure by standardizing data formats, developing an institutional clinical database in OMOP Common Data Model (CDM), integrating clinical-genomic visualization tools like cBioPortal, automating data workflows, and enhancing data accessibility and usability through tailored applications and ETL processes. Our DERU has created a robust system that helps us better organize, connect, and understand patient data. By standardizing how we collect information and making it easier for researchers to explore clinical and genomic data together, we are speeding up the development of more precise and personalized treatments. Tools like cBioPortal now help researchers visualize patient data in ways that highlight new insights into cancer.
  • The Bioinformatics Unit has strengthened collaborations across VHIO through 48 omics data analyses, expanded cluster infrastructure with GPU support for AI, developed standardized analysis pipelines, promoted data sharing via FAIR-aligned protocols, and fostered knowledge exchange through its monthly bioinformatics journal club.
  • VHIO and VHIR led the SYNTHIA breast cancer use case, with the ODysSey group spearheading a feasibility phase to define eligible populations and integrate multimodal data for synthetic data generation. Outcomes of this project may allow researchers to study and improve treatments for specific patient groups without compromising privacy and under the European Union data protection laws.

Significant data management advancements included launching an institutional Data Management Plan (DMP) template, setting internal data policies, appointing a Data Steward, initiating a data catalogue, and deploying the cVHIOportal as a new institutional tool for secure data sharing and visualization. This year, we implemented new internal policies to ensure responsible and effective data use. We introduced a dedicated Data Steward, launched a searchable data catalogue, and rolled out the first pilot of our cVHIOportal tool. The program achieved key technical advancements with expanded computational capacity for AI analyses, over 1PB of new storage infrastructure, and a streamlined catalogue of multi-omics analysis pipelines. The Biocomputational-Bioinformatics Journal Club, engaging 30–40 participants monthly in discussions on emerging topics and the Computational Oncology Master Thesis Award co-organized by the VHIO Academy, recognizing outstanding Master’s theses in Computational Life Sciences from Spanish universities, open to all nationalities.

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