Institutional Programs Supported by our Private Patrons

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 Precision Intelligence & Oncology Network For Enhanced Evidence & Research (PIONEER)
CaixaResearch Advanced Oncology Research Program (2020-2025)

In 2025, the CaixaResearch Advanced Oncology Research Program reached its final year, culminating a strategic partnership that has been instrumental in strengthening VHIO’s position as a leading European center in precision oncology, early-phase clinical research, advanced molecular diagnostics, and translational innovation. Throughout this final year, the support of ”la Caixa” Foundation, has continued to accelerate the integration of cutting-edge science into tangible clinical benefit for patients.

At the core of this program stands the Research Unit for Molecular Therapy of Cancer (UITM) CaixaResearch, directed by Elena Garralda. In 2025, UITM participated in 322 active phase I clinical trials, reinforcing its role as a reference unit for early drug development in oncology. During the year, 85 new studies were opened, over 1,300 patients were treated, and over 740 first visits were performed. The unit continued to participate in first-in-human studies and biomarker-driven trials evaluating highly selective targeted therapies, next-generation bispecific antibodies, and innovative agents directed at previously intractable oncogenic drivers. These efforts consolidate VHIO’s leadership in early-phase precision therapeutics and its capacity to translate molecular insights into clinical opportunities.

The UNIQUE-CaixaResearch platform for single-cell and spatial transcriptomics significantly expanded its operational capacity in 2025, conducting 23 single-cell and spatial transcriptomic experiments across multiple research groups, enabling deeper characterization of tumor heterogeneity, microenvironment interactions, and treatment response dynamics. The microscopy platform logged more than 700 hours of advanced imaging, reflecting sustained institutional demand. Dedicated training activities supported the uptake of these technologies, with 37 researchers receiving hands-on instruction and structured theoretical modules delivered through the VHIO Academy. This sustained growth and increasing strategic relevance led to the strengthening of its long-term integration within VHIO’s research infrastructure. Complementary investments in high-performance computational infrastructure and data integration tools have further reinforced VHIO’s digital transformation, enabling increasingly complex multi-omic analyses to inform precision oncology and clinical decision-making.

VHIO Academy, continued to play a central role in reinforcing scientific excellence and international visibility. In 2025, 17 VHIO-Caixa Research Scientific Seminars were organized, including national and international speakers, and achieving gender balance. Average attendance reached 78% capacity, reflecting strong engagement from the scientific community. These seminars, alongside competitive fellowship programs and international recruitment initiatives, continue to position VHIO as a dynamic hub for scientific exchange and talent attraction.

Outreach and societal engagement remained a priority throughout the year. VHIO’s communication initiatives continued to expand public understanding of precision oncology and advanced therapies, while amplifying the visibility of Fundación “la Caixa” as a key enabler of transformative cancer research. Media coverage, public engagement activities, and educational programs collectively reinforced the societal impact of this partnership.

Four CaixaImpulse projects remained active during the year, reinforcing the structured progression from discovery to commercialization. Entrepreneurial initiatives linked to VHIO continued advancing clinical and industrial translation, supported by a strengthened internal innovation management framework.

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 in innovation who have joined VHIO’s specialized Innovation Unit. This unit has played a central role in guiding research groups in the development of business plans and valorization strategies, enhancing the quality and impact of proposals submitted to external calls.

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 (PoC) funding. This funding is essential for conducting key experiments that inform the prioritization or de-prioritization of early-stage research, and it plays a pivotal role in advancing projects to a higher level of maturity, making them eligible for more substantial valorization programs. VHIO has steadily increased its capacity to secure such funding: in 2023, PoC grants totaled €555,630, followed by €443,800 in 2024. In 2025, this figure surpassed €1,000,000 for the first time—representing an 80% growth over the 2023–2025 period—underscoring VHIO's growing competitiveness in highly competitive innovation calls.

Building on projects already in the process of valorization—led by the Innovation Unit and supported through 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, which has proven critical for VHIO personnel, particularly postdoctoral researchers.

In terms of CaixaImpulse outcomes, VHIO had two active CaixaImpulse Explore (Phase I) projects from the 2023 call, led by Ana Vivancos and Rodrigo Toledo. In 2024, VHIO achieved a significant milestone with the awarding of a CaixaImpulse Consolidate (Phase II) project to Marcos Malumbres—a project that 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. This trajectory continued into 2025, with an additional CaixaImpulse Consolidate (Phase II) project awarded, further demonstrating the robust and maturing innovation pipeline fostered by the comprehensive and strategic support of the "la Caixa" Foundation.

As the CaixaResearch Advanced Oncology Research Program concludes in 2025, its legacy is firmly embedded within VHIO’s clinical platforms, molecular diagnostics infrastructure, innovative therapy capabilities, digital transformation, and innovation ecosystem. The structural support provided by Fundación ”la Caixa” has enabled not only the expansion of early-phase clinical activity and high-impact scientific production but also the consolidation of a sustainable model in which precision diagnostics, translational research, and therapeutic development operate in a fully integrated manner.

FERO Foundation Institutional Advanced Molecular Diagnostics Program (DIAMAV)

FERO Foundation: driving advanced molecular diagnostics against cancer

Our Molecular Prescreening Program is supported by Fundación FERO, one of VHIO’s Institutional Supporters and Patrons. Through FERO’s Institutional Advanced Molecular Diagnostics Program (DIAMAV), this initiative serves as a cornerstone of precision medicine at VHIO. Over the past decade, this program has enabled access to advanced molecular diagnostics to more than 12,000 cancer patients and plays a critical role in matching patients to targeted therapies through VHIO’s extensive portfolio of clinical trials.

The program is developed in close collaboration with the Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, 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. Coordination is provided by Susana Aguilar Head of the VHIOTECA Unit.

Our multidisciplinary team specializes on the clinical implementation of advanced molecular diagnostics to optimize therapy selection for patients considered for enrolment in clinical trials. By integrating molecular and pathological profiling, we identify actionable alterations and molecular risk factors that inform treatment decisions and trial eligibility within VHIO’s UITM - CaixaResearch. The program also provides continued medical education on emerging cancer biomarkers to support precision oncology practice.

In the last trimester of 2023, we launched a monthly Molecular Tumor Board (MTB). During these meetings we review and discuss the results of somatic next-generation sequencing (NGS) panels and other relevant biomarkers within the clinicopathological context of individual patients. Each discussion includes a focused literature review to assess the actionability of detected alterations. Two cases are reviewed per session, reinforcing structured, evidence-based decision-making.

Thanks to the support from FERO, our Molecular Prescreening Program has consolidated its position as a European reference in oncogenomics. In 2025, molecular profiling was performed in 2,529 patients across multiple cancer types. This number is more than double the annual average registered between 2014 and 2022 (approximately 1,100 cases).

Since 2023, we have implemented the VHIO360, our liquid biopsy panel developed in partnership with Guardant Health. Remarkably, in 2025 alone, 1,512 patients underwent testing with this platform. Initially reserved for cases with insufficient tissue, VHIO360 is now also routinely used to monitor emerging driver alterations associated with disease progression.

To further enhance diagnostic capabilities, the Genomics Laboratory replaced the NanoString platform with RNA sequencing. Introduced as the Epsilon test in late 2023 and adopted as our reference RNA-based assay in 2024, this approach improves detection of gene fusions and gene expression changes. These improvements are critical for identifying increasingly actionable cancer biomarkers, many of which have low prevalence (affecting less than 2% of patients), such as gene fusions. Additionally, in 2024, we initiated the development of a digital pathology biorepository to integrate imaging data with genomic, transcriptomic, and proteomic datasets, supporting advanced biomarker discovery.

In 2025, we implemented a new automated data management and notification system for prescreening results. By integrating pathology and genomics test orders, reporting workflows, and clinician alerts into a unified SQL database, we enhanced efficiency, traceability, and real-time communication. This integration was achieved through close collaboration between VHIO's Oncology Data Science (OdysSey) Group and the Data Engineering for Research Unit (DERU), led by Anna Pedrola.

FERO’s Institutional Program continues to be instrumental in driving these advances, enabling broader patient access to cutting-edge molecular technologies, accelerating liquid biopsy implementation, and strengthening VHIO’s leadership in early cancer detection and precision oncology.

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

Consolidating leadership in translational immunotherapy and advanced cell therapies

In 2025, the BBVA Foundation Comprehensive Program of Cancer Immunotherapy and Immunology (CAIMI-II) reached its final year, marking the successful consolidation of VHIO as a leading European center in translational immuno-oncology and advanced cellular therapies. Over the course of the program, CAIMI-II has integrated discovery science, biomarker development, clinical investigation, and manufacturing capabilities to advance more precise and effective immune-based cancer treatments.

Structured around two complementary pillars — fundamental immuno-oncology research and advanced adoptive cell therapies (PROTEA) — CAIMI-II has delivered high-impact scientific advances and enabled regulatory milestones.

A major scientific achievement of CAIMI-II has been the development of a robust framework to identify and prioritize tumor-reactive T cells directly from peripheral blood. Through single-cell RNA sequencing and longitudinal TCR profiling, VHIO researchers characterized how immune checkpoint blockade reshapes tumor-reactive clonotypes over time. These studies have revealed the dynamic evolution of T cells and enabled the generation of time-resolved gene-expression signatures capable of distinguishing tumor-reactive TCRs from the broader circulating T-cell repertoire. This approach supports scalable prioritization of clinically relevant TCRs without the need for repeated tumor biopsies, providing a conceptual and technical bridge between immune monitoring and next-generation personalized adoptive cell therapies.

CAIMI-II has also produced key insights into how tumor-intrinsic oncogenic programs influence immune responses. Comprehensive analyses in KRAS-driven non-small cell lung cancer demonstrated that high MYC activity is associated with immune suppression and reduced antigen presentation. Building on these findings, VHIO investigators have shown that MYC inhibition with OMO-103 not only suppresses oncogenic signaling but actively reshapes the tumor immune microenvironment. In patients deriving clinical benefit, on-treatment biopsies revealed induction of interferon signaling, TNF-family co-stimulatory pathways, and antigen presentation programs that are not observed in non-responders. These results, presented internationally throughout 2025, establish a strong translational rationale for combining MYC inhibition with immunotherapies and reinforce MYC’s role at the tumor–immune interface.

Another impactful translational contributions of CAIMI-II has been the validation of circulating tumor DNA (ctDNA) dynamics as a broadly applicable biomarker across solid tumors treated with immunotherapy. Published in Clinical Cancer Research, this study demonstrated that ultrasensitive ctDNA monitoring across 24 tumor types enables early prediction of treatment benefit, improved survival stratification, and more accurate differentiation between true progression and pseudoprogression —an enduring clinical challenge in immunotherapy. The work has drawn substantial national and international attention and has positioned VHIO at the forefront of minimally invasive, precision-guided oncology. Building on this platform, nearly 2,000 plasma-derived genomic datasets have been generated, and an integrated digital tool is being developed to combine ctDNA kinetics, imaging data, and clinical parameters to support real-time monitoring in early-phase trials.

Under the PROTEA pillar, CAIMI-II has significantly strengthened VHIO’s advanced cell therapy portfolio. A key innovation has been the development of minimally invasive strategies to generate personalized T-cell therapies from peripheral blood. Analysis of whole-exome sequencing data from 77 patients indicates that approximately half of patients with advanced epithelial cancers could potentially benefit from this approach, representing an important step toward the clinical implementation of blood-derived personalized T-cell therapies. In parallel, VHIO has continued advancing tumor-infiltrating lymphocyte (TIL) strategies, contributing to the growing clinical evidence base, including a systematic review and meta-analysis published in Annals of Oncology confirming the safety of adoptive TIL therapy combined with high-dose interleukin-2 in advanced melanoma.

A major regulatory milestone was achieved with the p95HER2.CAR-TECH2Me program. This highly selective CAR-T strategy targets the tumor-specific p95HER2 isoform while minimizing off-tumor toxicity. Following extensive preclinical validation in multiple patient-derived xenograft models, the phase I clinical trial was approved by the Spanish Agency for Medicines and Health Products (AEMPS) in December 2025, with patient recruitment expected in 2026. This approval marks a decisive transition from laboratory innovation to clinical reality and underscores VHIO’s growing capabilities in advanced therapy development.

Through the BBVA Innovative Research Grant, CAIMI-II also supported the development of a fully humanized monoclonal antibody targeting a cytokine-signaling co-receptor implicated in myeloid-driven immunosuppression. Preclinical studies demonstrated anti-tumor activity across multiple orthotopic models, including glioblastoma, and showed synergy with adoptive cell therapies without apparent toxicity. A priority intellectual property filing was submitted in 2025, reinforcing the translational and commercial potential of this novel immunomodulatory strategy.

The program has generated a strong portfolio of high-impact publications across leading journals, including Clinical Cancer Research, Cancer Research, Annals of Oncology, among others, reflecting advances in biomarker development, immune resistance mechanisms, and emerging immunotherapy targets. These scientific outputs have been complemented by extensive international dissemination, including invited presentations at major congresses and the 2nd VHIO–BBVA Foundation International Symposium on Cell-Based Therapies in Oncology, which convened 350 participants from leading global institutions. BBVA Foundation-supported undergraduate, master’s, and MD-PhD fellowships have further strengthened VHIO’s commitment to training the next generation of clinician-scientists in immune oncology.

As CAIMI-II concludes, its scientific discoveries, regulatory achievements and talent development initiatives remain fully embedded within VHIO’s research ecosystem. By integrating mechanistic immunology, innovative biomarkers, advanced cellular therapies, and clinical translation, the program has established a sustainable platform to accelerate the development of more precise and effective immune-based cancer treatments. Building on this momentum, a new four-year agreement has been signed with the BBVA Foundation to launch CAIMI–III in 2026, ensuring the continuity and further expansion of this strategic program and reinforcing VHIO’s long-term commitment to advancing next-generation cancer immunotherapies.

VHIO-CRIS Precision Intelligence & Oncology Network For Enhanced Evidence & Research (PIONEER)

The VHIO-CRIS PIONEER program is advancing personalized cancer medicine by supporting biomedical and clinical research, with a clear focus on delivering tangible benefits for patients. This program is designed to leverage the strategic expansion of research groups on data sciences and computation, the implementation of breakthrough technologies, and the exponential growth of biomedical data that enables formulating new hypotheses to address critical challenges in oncology.

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 Statistics 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 2025:

  • Over the past year, the Statistics Unit has participated in the design or analysis of >10 clinical trials and contributed to 22 Q1 scientific publications. It has also advanced biomarker validation, applied complex statistical methodologies, and engaged in national and European projects focused on innovative trial designs to improve VHIO’s oncology research. Additionally, during 2025, the unit has initiated cost-effectiveness projects to integrate quality-adjusted overall survival and cost metrics into clinical decision-making, reinforcing its commitment to delivering high-value, evidence-based care.
  • The Data Engineering for Research Unit (DERU) has consolidated VHIO’s institutional data infrastructure. Building on the implementation of the OMOP Common Data Model (CDM), DERU now enables harmonization and integration of clinical and multi-omics data through interoperable platforms. The cVHIOportal provides multidimensional visualization of cancer data aligned with treatment information and currently supports 34 research projects, integrating data from 3,325 patients and 3,618 samples.
  • DERU has also strengthened institutional data governance by reinforcing quality assurance processes through REDCap (eCRF) validation in compliance with EU and FDA regulatory requirements. Through automated ETL pipelines, tailored applications, and multimodal integration capabilities DERU provides a robust, standardized and regulatory-ready ecosystem that accelerates translational research and precision oncology innovation at VHIO. One example is the integration of OncoPharma database (exposure to systemic anti-cancer therapies) to the clinical-molecular repositories managed by DERU. With support from the Oncology Data Science (ODysSey) Group, the data are being qualified so that all patients have pharmacy records added as another layer of information in the exploration and analytics process.
  • The Bioinformatics Unit has strengthened collaborations across VHIO through fifty-eight data analyses. The study set comprised mainly transcriptomics and genomics data, but it was enriched by shotgun metagenomics projects to explore the tumor micro-environment. We also performed reassessment of several publicly available datasets to gain insights into the development and spread of cancer. With the recent onboarding of single-cell technologies and expertise, we are now analyzing several transcriptomic and multi-omics single-cell experiments. In addition, the Unit has overseen the expansion of the computational cluster infrastructure, adding more resources and 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 continue to lead the SYNTHIA breast cancer use case, with the CRIS-supported Oncology Data Science (ODysSey) group advancing multimodal data integration for synthetic data generation (SDG). In 2025, ODysSey has harmonized clinical records mapped to common cancer data models and integrated them with radiology (MMG, MRI) and digital pathology data. Nearly 2,000 patients have been identified as eligible, with approximately 1,500 radiology datasets and 1,000 digitized pathology images available for integration. This milestone strengthens privacy-preserving multimodal research and accelerates biomarker discovery and precision oncology innovation under EU data protection standards.

Significant data management advancements include launching an institutional Data Management Plan (DMP) template, setting internal data policies and appointing a Data Steward, initiating a data catalogue. 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 stands as a key initiative, engaging 30–40 participants monthly in discussions on emerging topics.

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