Action 1 – Project Management
Action Lead: FRCB-IDIBAPS.
Action Objective: Comprehensive project management.
The administrative management, coordination, and internal communication of the project, along with its monitoring and evaluation, will be led by FRCB-IDIBAPS. A part-time manager, supported by the project management office, will maintain a contact directory, coordinate information flow, review financial and technical reports, ensure the quality of deliverables, track project milestones, coordinate partner payments, and manage budget risks. Internal communication will involve establishing a communication protocol, convening follow-up meetings, and distributing minutes for partner approval. Incident management will include drafting contingency measures and documenting meetings. Financial management will cover expense reporting, reimbursement requests, quality control of financial statements, and reviewing technical reports. Budget deviations will be anticipated through clarification requests and audits, and proper allocation of expenses for equipment, consumables, travel, and personnel will be monitored. Internal milestones will be established, and contingency measures drafted. The action plan management will be reviewed at biannual partnership meetings, aligning deliverables and indicators with expense declarations.
Action 2 – Communication
Action Lead: FRCB-IDIBAPS.
Action Objective: Disseminate THERAVLINFO’s objectives and results on advanced therapies for the treatment of NHL, its socio-economic impact on biomedicine, and patients’ lives.
Target Audience: Lymphoma patients and their families, the scientific Hemato-Oncology community, the general public interested in health and well-being, and students of biomedical disciplines.
To achieve wide visibility and support for THERAVLINFO and the POCTEFA Program, audiovisual communication through the internet and social media will be employed, engaging specialized and general media, and promoting the program’s logos and symbols. This activity will strengthen project partners by positioning them as leaders in Hemato-Oncology, 3D organoid platform biotechnology, preclinical models, and nanoparticle formulation. Dissemination through conferences, scientific publications, the web, social media, and outreach events will create new opportunities for collaboration with cross-border partners and companies. Regular meetings, both in-person and virtual, will be held to share progress and important decisions, promoting constant collaboration and open dialogue between team members. Communication will be key for results transfer, using digital media, specialized journals, conferences, and other relevant platforms in Hemato-Oncology. Educational material for patient associations, hospitals, and educational centers will also be developed to ensure long-term sustainability and transmission. The goal is to provide transparency and relevance to THERAVLINFO’s scientific-technical activities and encourage community participation and engagement. A constant dialogue between partners will identify needs and opportunities for improvement. Specific actions include a promotional video, outreach to patient associations and civic centers using sketchbook techniques, scientific publications, and presenting results at conferences.
Action 3 – Maintenance and Generation of Preclinical NHL Models (in vitro, ex vivo, and in vivo)
Action Lead: FRCB-IDIBAPS.
Action Objective: Generate preclinical models of aggressive, relapsed, or refractory NHL: 1) creation of a 3D repository of 50 primary tumors resistant to standard therapy or relapsed, 2) murine models of aggressive NHL for validation of top therapeutic candidates.
The project aims to develop preclinical models of non-Hodgkin lymphoma (NHL) that reflect complex clinical scenarios, such as relapsed or refractory (R/R) patients, where new molecules will be tested. Optimized protocols (Arauyo-Ayala et al., Leukemia 2023; Dobaño-López et al., Blood 2022; Gava et al., Cancers 2021; Faria et al., J Immunother for Cancer 2023, in revision) will be used to create 3D models integrating the tumor microenvironment of R/R NHL patient cells. Anonymous samples will be provided by HCB and CHU, with associated clinical data and genomic characterization at each center.
IMLINFO’s 3D models will be improved by adding elements of the tumor microenvironment, crucial for immune and therapeutic responses. LNH microenvironment cells will be incorporated to better reflect tumor biology. Additionally, in collaboration with the University of Navarra, murine models of aggressive NHL, validated in previous studies (Pascual et al., Blood 2019; Melchor et al., J Immunother Cancer 2023), will be added to confirm target expression identified in IMLINFO. While the reduction of animal use in experimentation (3Rs) is valued, validation in animal models remains essential for clinical translation.
Action 4 – Lead Selection and Drug Development for Blocking/Inhibiting a Panel of Tumor Targets Identified in the Previous IMLINFO Project
Action Lead: FRCB-IDIBAPS.
Action Objective: Develop and share new antibodies or cellular therapy (CAR-T CD19-CD70) among THERAVLINFO partners, formulated as free antibodies or encapsulated in nanoparticles for improved oral bioavailability in vivo.
The project focuses on lead selection and drug development to block or inhibit tumor targets previously identified in the IMLINFO project. The objectives include developing and sharing antibodies or cell therapies formulated as CAR-T or encapsulated in nanoparticles to improve oral bioavailability in vivo. Comparative gene expression analysis from the IMLINFO project identified overexpressed molecules in NHL involved in specific tumor metabolism and microenvironment processes.
Therapeutic antibody generation will be outsourced to ONA Therapeutics, a spin-off with experience in this field. One main challenge is designing oral delivery systems to avoid continuous intravenous administration. In collaboration with NUCAPS, therapeutic antibodies will be encapsulated in gastro-resistant nanoparticles to assess their oral efficacy. Studies include release in simulated media, biodistribution in mice, and comparative pharmacokinetics with intravenous administration. Additionally, CAR-T generation will be conducted at HCB/IDIBAPS, utilizing their experience and equipment to produce CAR-T cells.
Action 5 – Evaluation of Efficacy and Therapeutic Response of Molecules and Innovative Technologies Developed Within the Consortium
Action Lead: University of Navarra.
Action Objective: Study the efficacy and mechanisms of action of the various drugs synthesized within the THERAVLINFO network, evaluating their therapeutic potential in different preclinical models (in vitro and in vivo) that replicate the complexity of the human lymphoma tumor microenvironment.
This research aims to evaluate the efficacy and mechanisms of action of drugs developed by the THERAVLINFO network, examining their therapeutic potential in preclinical in vitro and in vivo models that simulate the human lymphoma tumor microenvironment. The goal is to synergize partners’ expertise in immunotherapy, cell and molecular biology, nanoparticle chemistry, bioinformatics, and animal experimentation to validate the therapeutic and translational potential of new targets and advanced therapies against NHL. Hospitals CHU and HCB will contribute to interpreting drug efficacy results in organoids and designing preclinical mouse studies, helping to correlate clinical, biological, and genomic data between organoids and NHL patients. Expert centers UPS and IDIBAPS will test the advanced therapies in vitro, characterizing their efficacy and mechanisms of action, and collaborate with UNAV in designing in vivo trials, validating the drugs’ therapeutic potential in animal models.
Action 6 – Training and Mobility
Action Lead: University of Toulouse III Paul Sabatier-CRCT.
Action Objective: Facilitate access to employment and high-quality training for students through (i) integrating them into THERAVLINFO’s research groups and (ii) promoting their mobility among network members once established as predoctoral researchers.
The THERAVLINFO initiative seeks to facilitate access to employment and high-quality training for students by integrating them into research groups and promoting their mobility among network members once established as predoctoral researchers. This cooperative training and mobility action will result in knowledge exchange, methodologies, protocols, and expertise in hemato-oncology and biotechnology, access to equipment and infrastructure across institutions, joint use of reagents (advanced therapies), and community participation in evaluating and interpreting results with high translational value. The network’s university centers (IDIBAPS, UPS, and UNAV) will co-supervise at least three doctoral students, one at each center, offering the possibility of obtaining European Doctorates from the Universities of Barcelona, Toulouse, and Navarra. THERAVLINFO partners will offer short stays for predoctoral researchers, managing co-supervision and co-direction through quarterly meetings, including two in-person and two teleconferences per year. To enhance the training impact, the program will be opened to Master’s and undergraduate students, allowing them to conduct their final projects in the university centers’ laboratories. Additionally, THERAVLINFO will participate in workshops and visits for secondary, high school, and vocational students, satisfying their curiosity about the diverse research lines in the POCTEFA area.