Institutional Programs Supported By Our Private PATRONS
”la Caixa” Foundation: advancing research to drive precision THERAPEUTICS
Continuing the trajectory of success from the previous two VHIO – ”la Caixa” Institutional 3-year Programs, 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 frontier research in precision oncology. The patronage of the ”la Caixa” Foundation has significantly contributed to accelerating progress against cancer.
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 resistance mechanisms to anticancer therapies. To this end, the UITM leverages 'big data'-derived insights and integrates cutting-edge platforms, incorporating bioinformatics, biostatistics, and machine learning applications in cancer prognosis and prediction. Reflective of its unwavering commitment to innovation and precision oncology, the UITM also harnesses the potential of artificial intelligence (AI) for the development of individually matched therapies – getting the right therapy to the right patient at the right time.
Early phase clinical trials conducted at the UITM have played a pivotal role in advancing precision medicine in oncology, leading to the approval of over 30 anti-cancer agents by regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). VHIO groups and teams, including Early Clinical Drug Development, Cancer Genomics, Molecular Oncology, and Oncology Data Science – OdysSey, led by Elena Garralda, Ana Vivancos, Paolo Nuciforo, and Rodrigo Dienstmann, respectively, contribute their expertise to drive these efforts.
In 2023, our unit participated in 249 phase I clinical trials with active recruitment at some time in the year, 25 of which are Basket studies. Thanks to our multidisciplinary team, we have continued to expand our portfolio of phase I and Basket trials, with 608 patients enrolled. This year, we opened 55 new studies, treated over 1,250 patients throughout the year, and performed over 600 first visits.
A key component of our CaixaResearch Advanced Oncology Research Program is the UNIQUE CaixaResearch platform (UNderstanding cancer through sIngle cell seQUEncing). This new transversal platform for next generation single-cell sequencing is designed to explore gene expression in tumor tissue and blood samples, allowing for the characterization of expression patterns in individual cells. The platform integrates three state-of-the-art devices that are integrated into VHIO's core cross-cutting technology platforms, including Parsortix technology for isolating circulating tumor cells from liquid biopsies, and the Chromium X equipment (10x Genomics) for single-cell analyses. It also has a Leica DMi8 microscope equipped with Thunder technology and a CytAssist device (10x Genomics) for mapping individual cells in solid tumor samples, understanding their spatial distribution and interactions with their environment, and deciphering their patterns of gene expression within their tissue context.
FERO Foundation Institutional Advanced Molecular Diagnostic Program (DIAMAV)
FERO Foundation: driving advanced molecular diagnostics against cancer
Our Molecular Prescreening Program is powered by one of our Patrons, the Fundación FERO. FERO’s Institutional Advanced Molecular Diagnostics Program (DIAMAV) catalyzes precision medicine at VHIO. Over the last decade, this program has provided 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 focuses on the clinical implementation of advanced molecular diagnostics to optimize the selection of therapies for patients being considered for enrolment in clinical trials, as well as continued medical education on emerging cancer biomarkers for precision cancer therapy. By advancing molecular profiling in patients, personalized treatment strategies based on the genomic or pathologic profile of each individual patient can be more effectively matched to the molecular makeup of their respective disease.
Our researchers and clinical investigators identify specific molecular risk factors and predictors of efficacy of specific agents tailored to each particular tumor. These insights guide our multidisciplinary teams to assess and establish the patients’ suitability for enrolment in early phase clinical trials conducted at VHIO’s UTIM – CaixaResearch.
As a highlight, at the last trimester of 2023 we implemented a new monthly Molecular Tumor Board where we discuss the results of targeted NGS panels and other biomarkers within the clinicopathological context of each individual patient, incorporating a thorough review of the literature to support interpretation of variants and their actionability with targeted therapies. In each MTB we discuss two patients.
It is thanks to the backing received from FERO that our Molecular Prescreening Program continues to be a reference in oncogenomics in Europe. Thanks to our cutting-edge technologies and platforms, we continue to extend the promise of precision medicine in oncology to an increasing number of individuals. In 2023, we have implemented for the first time the VHIO360 panel, our liquid biopsy technology in partnership with Guardant Health, that allows tumor molecular profiling from blood samples. Our growing efforts to better characterize tumors have resulted in the molecular profiling of 1,968 cancer patients’ tumors, representing a substantial increase over previous years.
In short, FERO’s Institutional Program contributes to run such a comprehensive program. In so doing, we continue to ensure that more of our patients can ultimately benefit from our precision medicine approaches.
BBVA Foundation: generating new insights into the mechanisms of resistance and response to immune-based therapies
In 2023, the first BBVA Foundation Comprehensive Program of Cancer Immunotherapy and Immunology (CAIMI) concluded, marking the start of its second edition, CAIMI-II. CAIMI-II focuses on advancing immuno-oncology (IO) and developing novel immunotherapies against cancer. Thanks to the funding received from the BBVA Foundation, VHIO teams including our Tumor Immunology and Immunotherapy and Growth Factors Groups, led by Alena Gros and Joaquín Arribas, respectively, are investigating new cellular products including tumour-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cells, among others.
Through this program, VHIO is rapidly becoming a European reference in the design and development of comprehensive, translational studies in IO and cancer immunotherapy, particularly in early clinical drug development. We lead several innovative studies including the phase I NEXTGEN-TIL trial. Conducted in collaboration with Alena Gros, this study was designed to evaluate the safety and tolerability of neoantigen-selected TIL therapy in patients with metastatic or unresectable epithelial cancer and patients with solid tumors resistant to immune checkpoint inhibitors (ICIs). Our results investigating immune evasion through leukemia inhbitory factor (LIF) activation in cervical cancer, set the rationale for combining anti-LIF antibodies with ICIs in these patients. Results of another study involving 153 patients with head and neck squamous cell carcinoma (HNSCC), indicate that poor nutritional status is a robust prognostic biomarker associated with lack of response to immunotherapy.
Another important development has been the external validation of our VIGex signature for immunotherapy. This signature classifies solid tumors based on the expression of immune-related genes, representing a valuable, predictive tool for refining patient selection for early-phase immunotherapy clinical trials. This tool, derived from an optimized gene signature of 12 key genes involved in immune response, is the result of an international collaboration, involving over 1,000 tumor samples across 45 different cancer types.
Within this program, we are also investigating personalized, minimally-invasive T-cell therapies guided by whole-exome sequencing (WES) analysis of circulating free DNA (cfDNA) in patients, aiming to expose neoantigens. The data suggests that cfDNA can effectively capture neoantigens targeted by circulating T cells, providing valuable insights for the development of T cell therapies obtained from peripheral blood. TCR gene-engineered T cells proved successful in identifying T cells recognizing specific mutations, highlighting the therapeutic potential of non-canonical sources of tumor antigens. These findings open new avenues for the development of cancer immunotherapies.
In the realm of CAR-Ts and BiTEs, modifications were implemented to CAR constructs to enhance efficacy, and affinity-tuned antibodies were developed for precise tumor targeting. The team is engaged in a highly complex trial in collaboration with the University of Navarra involving allogenic natural killer cells (NKs) in combination with trastuzumab and pertuzumab for refractory metastatic HER2-positive breast cancer.
The strengthening of VHIO's Advanced Therapies Program has been recognized by a grant to support the ARES trial, focusing on germ cell tumor therapy based on autologous tumor-infiltrating lymphocytes. Additionally, several other projects are either underway or in preparation, highlighting the ongoing commitment to advancing therapeutic interventions.
CAIMI also supports several educational and training opportunities including the Mobility Fellowships for IO Medical Researchers at VHIO. These fellowships enable physician scientists to pursue translational research through international internships. This program aims to provide training on specialized research skills, expand researchers' networks, promote the internationalization of VHIO, and facilitate the career progression of fellows. Notably, successful clinical exchanges have already taken place at renowned institutions including the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, and the University College London (UCL). Additionally, our International Secondment Fellowships for clinical residents and doctoral researchers, provide opportunities for up to three-month secondments in international cancer research institutions, and our Undergraduate Fellowships program aims to introduce university students to research in the field of immunology.
Lastly, we organized the 1st VHIO-BBVA Foundation International Symposium on Cell-based Therapies in Oncology, 29-30 November at the Ateneu Barcelonés cultural center in Barcelona. This event provided an outstanding forum to present and the very latest developments in the field of advanced cell therapies, and to foster collaboration among leading, international experts. This meeting was organized by VHIO’s Alena Gros together with Sònia Guedan at the Clínic Barcelona - August Pi i Sunyer Biomedical Research Institute (IDIBAPS).
INSTITUTIONAL SUPPORT BY OTHER FUNDING BODIES
Severo Ochoa Center of Excellence (2022-2026)
Programa Centro de Excelencia Severo Ochoa: strengthening VHIO research programs and teams in advancing cancer discovery and precision medicine in oncology
Since 2022 our institute is accredited as a Severo Ochoa Center of Excellence (2022-2026). This prestigious distinction is granted within the subprogram of the Spanish Institutional Strengthening of the State Plan for Scientific and Technical Research & Innovation and is managed and supported by the Agencia Estatal de Investigación* - AEI (Spain’s State Research Agency), a body affiliated with the Ministerio de Ciencia e Innovación (Spanish Ministry of Science and Innovation).
This distinction recognizes national research centers that demonstrate scientific leadership of excellence and impact at global level and is renewable each 4 years through re-application under the same rigorous independent evaluation carried out by an international scientific committee. VHIO is the first research institute linked to the national healthcare system to receive this distinction.
This award reflects our Institute’s important contributions to cancer science and precision medicine in oncology at a global level. It also confirms VHIO’s scientific leadership and proven capacity to advance research, generate high-impact results, as well as attract and retain research talent.
This VHIO Institutional Program further strengthens our various research programs and teams in driving important advances in cancer discovery and precision medicine in oncology.
The new cross-cutting Severo Ochoa Digitalization Unit (SOUND) lies at the intersection of digital health and data science for research, clinical applications and patient-centered medicine. This Unit aims to accelerate the development and implementation of data science models and technology platforms in healthcare for personalizing patient care at VHIO and in synergy with existing alliances (CCE and others). Since 2022, SOUND has launched the cVHIOportal for cancer genomics adapted to research data at VHIO, has created a new Head of IT position within the Institution to further advance our data infrastructures and capabilities.
In 2023, the PAtients and CiTIzen InvolvemENT Program (PATIENT program), hosted 10 VHIO Talks involving 10 patients and 20 investigators on the discussion panels and reaching a total of 400 attendees. The PATIENT Program also hosted the Research Day for patient associations of breast cancer that gathered 8 associations, 5 investigators and more than 50 attendees, to talk about the advances and results of research done at VHIO. These activities are also important to bring together patients associations and the researchers to understand their perspectives on the research being done at VHIO.
The mission of the VHIO Academy, is to attract and train the next generation of scientific leaders in oncology. Since its creation, VHIO Academy has achieved several highlights including the launch of international Academic Programs (Bachelor, Master, PhD calls), the implementation of a structured International PhD Program and the deployment of an Advanced Training Program. In the period 2022-2023, VHIO Academy has consolidated the VHIO International PhD Program (+ 100 PhD students) adhering to the principles of interdisciplinarity and internationality, early independence and scientific creativity, excellence in science and technology, collaboration, and mentoring. Another highlight is the implementation of the e-Learning tool VHIO Moodle as versatile platform for training at VHIO.
Since the accreditation of VHIO as a Severo Ochoa Center of Excellence, 22 PhD fellows, 16 Master Students and 15 Summer Interns from 12 different countries have joined 21 research groups through the Academic Programs following Open, Transparent, Merit-Based (OTM) recruitment processes implemented by VHIO Academy.
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*Supported by the State Agency for Research - Agencia Estatal de Investigación - AEI (CEX2020-001024-S / AEI / 10.13039 / 501100011033).
AECC Excellence Program - Advanced Therapies Accelerator Program
Announced in December 2022, and now launched as one of VHIO’s Institutional Programs, we received the support from the Asociación Española Contra el Cáncer – AECC (Spanish Association Against Cancer) Excellence Program - Advanced Therapies Accelerator Program. This partnership aims to establish VHIO as an international reference in the emerging field of gene and cell therapies and to contribute to Europe’s advancement in this field.
To boost the development of academic gene and cell therapy products, along with translational and clinical research, we are providing our teams with the necessary training, promoting national and international collaborations, and establishing a robust governance structure. We are planning the initiation of the construction of the Advanced Therapies Accelerator Unit's clean room in 2024. These initiatives will facilitate the creation of new gene and cell therapy products and advance existing ones in our pipeline.
In 2023, as part of the Health Research Campus, VHIO secured funding as part of the national network for Advanced Therapy Medicinal Products (ATMPs) (CERTERA), fostering collaborations among national centres. Additionally, our team obtained international funding from the European Commission for two collaborative projects in ATMPs: the PragmaTIL and the JOIN4ATMP projects.
Our translational research teams are developing new tumor infiltrating lymphocytes (TILs) and chimeric antigen receptor T-cell (CAR-T) products. For TILs, we have established a method to select neoantigen (NeoAg) reactive TILs without the need for cell sorting. For CAR-Ts, we have patented a new p95HER2 CAR and are seeking approval from the Spanish Agency of Medicines and Medical Products (AEMPS) for advancing to clinical trials.
The Advanced Therapies Accelerator Unit – Clean Room, has developed an Exploitation Plan aiming for positive returns by 2027-2028.
We extend our gratitude to the AECC for its longstanding support of VHIO’s groups and researchers. In 2023, two of our investigators received awards from two of AECC’s funding programs.
Irene Braña, Principal Investigator of the Head and Neck Cancer Group, was awarded with the funding program Ayuda Estudios Clínicos AECC to perform the PROLoNg study: Pembrolizumab and Radiotherapy for OLigometastatic squamous cell carcinoma of the head and Neck: a randomized phase III study.
Through the ERA-NET program, the AECC and the Instituto de Salud Carlos III – ISCIII (Carlos III Health Institute) funded the project Systemic immunological determinants of tumor evolution and therapy response in BRCA-mutated pancreatic cancer (SIMMBAP) led by Teresa Macarulla, Head of the Upper Gastrointestinal and Endocrine Tumors Group at VHIO. The SIMMBAP consortium combines experts in clinical, fundamental, and computational cancer research, aiming to analyze changes in circulating and intratumoral immune cells in patients at high risk of pancreatic cancer, harboring mutations in the BRCA1/2 genes.
AstraZeneca José Baselga Innovative Disruption (J-BID) Program
The legacy of José Baselga, VHIO’s first and Founding Director, continues to inspire the next generation of cancer researchers and clinical investigators.
To honor his outstanding career and contributions to cancer research, the AstraZeneca José Baselga Innovative Disruption (J-BID) Program launched in 2022. This initiative embodies the spirit of disruptive innovation which epitomized José Baselga’s work and vision.
In 2023, the J-BID Program provided support to four VHIO groups leading projects with high potential for breaking new ground in our understanding of cancer and exposing novel actionable insights:
- A study led by Marcos Malumbres, co-Director of VHIO’s Preclinical and Translational Research Program and Head of VHIO’s Cancer Cell Cycle Group , is focusing on the development of next generation of cyclin-dependent kinase (CDK) inhibitors.
- A project directed by Joan Seoane, co-Director of VHIO’s Preclinical and Translational Research Program and Head of our Gene Expression and Cancer Group, is optimizing a patient-derived tissue culture platform to investigate new anticancer immunotherapies and identify predictive biomarkers of response.
- Research headed by Mate Maus, Group Leader of Aging and Cancer at VHIO, is investigating the underlying mechanisms and therapeutic potential of aberrant iron accumulation in early-onset colorectal cancer.
- A study directed by Francisco Barriga, Head of our Cancer Genome Engineering Group, is applying cutting-edge genome engineering techniques to characterize the role of copy-number alterations in the progression of pancreatic cancer and resistance to therapy.
Collectively, these innovative projects are reflective of VHIO and AstraZeneca’s unwavering commitment to supporting pioneering research that paves the way for new discoveries of high translational potential, and contribution to attracting and consolidating exceptional scientific talent in Spain.
TASK FORCES
VHIO’s multidisciplinary teams work together in dedicated Task Forces (TFs), coordinated by VHIO’s Scientific Management Area, that have been established based on VHIO’s strategic vision and core research priorities.
These dynamic teams bring together a diverse array of professionals including preclinical and translational researchers, clinical investigators, medical oncologists, pathologists, other medical disciplines, clinical research nurses, data specialists, study coordinators, and project managers.
Our TFs regularly convene to tackle various tumor types including breast, colon, gastroesophageal, kidney, neuroendocrine, rectal, pancreatic, prostate, and biliary tract cancers, with teams also dedicated to oncology imaging as well as patient engagement in research. By fostering collaboration and continuously refining protocols and ethical guidelines, our TFs drive advances in cancer science and precision oncology.
The structure of TF varies depending on size, workflow, participants, and level of activity. An appointed Chair leads each TF, supported by a project manager responsible for setting agendas, compiling meeting minutes, following up on action points and tasks, and promoting interaction and synergies across VHIO's TFs.
Illustrative of VHIO’s dedication to collaborative research, clinical investigators from diverse medical specialties within Vall d’Hebron and local hospitals in Catalonia, as well as translational researchers from the Vall d’Hebron Barcelona Hospital Campus and other research institutions, also actively participate in our TFs.
We are constantly working to identify new areas that might also benefit from specific task teams. In 2023, we established a new transversal TF focused on cancer prevention and early detection. Furthermore, a TF dedicated to patients has enabled the creation of our PAtient and CiTIzen InvolvemENT Program, which seeks to update and educate patients and the public at large on the latest research advances and empower patients regarding treatment decision making. Activities include the Vall d’Hebron Cancer Talks by VHIO themed ¿Hablamos sobre investigación y tratamiento del cáncer? (Shall we talk about cancer research and treatment?).
In 2024, we also envisage setting up new TFs and plan to further strengthen the involvement of patients in our research, especially in the development of clinical trials.