Team 5

Design and application of innovative loco-regional Treatments in Glioblastoma

Team leader : Emmanuel Garcion

Contact us

Emmanuel Garcion
Nantes-Angers Research Center for Cancer and Integrated Immunology
Institut de Recherche et d’Ingénierie de la Santé - 4 Rue Larrey 49100 Angers

+33 (0) 2 44 68 85 43
emmanuel.garcion@univ-angers.fr

Summary of the research:

In the context of treatment resistance in devastating solid tumors, the GLIAD team develops innovative local therapies for glioblastoma (GB), addressing an urgent unmet clinical need. We combine health technologies with mechanistic insights to overcome resistance and suboptimal drug delivery, while identifying novel targets, including oncogenic fusions and RNA-based interventions delivered via proprietary vectorization tools (aptamers, siRNAs, ASOs). These strategies are tested in orthotopic tumor-in-place and intracavitary rodent models, in vitro 3D systems, tumoroids and organotypic slices, within a federative research structure and coordinated platforms alongside a hospital-based environment, ensuring efficient translational pathways.

Our research follows two complementary axes:
i) AXIS-1: Locoregional vectorized radiation & theranostic strategies for GB focuses on vectorized radiotherapy with in situ radiosensitization to overcome intrinsic resistance and modulate the microenvironment. Building on β-emitting radiopharmaceuticals, we recently achieved unprecedented results with α-emitting 211At-mAb targeting syndecan-1, inducing 70% GB remission, reduced secondary foci, and long-term immune protection. Studies explore combinatorial strategies with miRNAs, immunostimulatory agents, and theranostics, optimizing target, carrier, and radionuclide selection, while oncogene fusions are evaluated as precision targets. ii)
AXIS-2: Precision polymer interventional implants for controlling GB progression & recurrence centers on implants that modulate the microenvironment to prevent post-resection relapse. Using biopolymer aerogel sponges loaded with chemoattractants, we guide directional GB cell attraction and the development of nanostructured hydrogels for delivery of nucleic acids and therapeutics within resection margins. These activities are driven by a multidisciplinary team within a strong international network. By combining mechanistic insights, innovative technologies, and translational strategies, GLIAD strengthens the field’s capacity to move beyond traditional approaches and meaningfully improve GB outcomes, positioning its work at the forefront of global efforts to transform this devastating disease.

Keywords: Locoregional treatment of GB; innovative therapies; vectorized radiation therapy; interventional nanostructured bio-implants; oncogene fusions & RNAi; therapeutic proteins, peptides & ODNs; MedTech.

Emmanuel Garcion, DR Inserm

Florian Bernard MCU-PH
Frank Boury, PU
Olivier Couturier, PU-PH
Florence Dumas-Giteau, MCU
François Hindré, MCU
Franck Lacoeuille, PU-PH
Jean-Michel Lemee, MCU-PH
Zeina Msheik, ATER
Audrey Rousseau, PU-PH

Laetitia Basset, IR CHU
Anne Clavreul, IR CHU
Clara Rapenne, TR Inserm
Charlotte Roy, IE UA
Laurence Sindji, AI Inserm

Mathis Barbotin, PhD Student
Abel Dambrain, PhD Student
Héloïse Dufour, PhD Student
Alix Fontaine, PhD Student
Prince N'Dlozi, PhD Student
Morgane Tomaz de Oliveira, PhD Student

Lucien Brunet, Interne titulaire d'un master 2
Julie de Miras, Master 2

Selected recent publications (last years)

Loussouarn C^#, Roncali L^#, Etcheverry A, Roy C, Clavreul A, Lacoeuille F, Rousseau A, Lemée JM, Menei P, Karayan-Tapon L, Mosser J, Hindré F, Baril P*, Garcion E*. MiR-22-3p shapes glioblastoma radiation resistance and 1 downregulates the DNA demethylase tumor suppressor TET1. Journal of Experimental & Clinical Cancer Research. (2026) in press. ^#,*Equivalent contributions. doi: 10.1186/s13046-026-03841-0.

Roncali L, Hindré F, Samarut E, Lacoeuille F, Rousseau A, Lemée JM, Garcion E*, Chérel M*. Current Landscape and Future Directions of Targeted-Alpha-Therapy for Glioblastoma Treatment. Theranostics, 15 (11) (2025) 4861-4889. *Equivalent contributions. DOI: 10.7150/thno.106081.

Rinaldi A, Kluczka E, Louis Fathy Nazir M, Barbotin M, Roy C, Basset L, Avril S, Anthiya S, Tosi G, Jérôme C, Boury F, Rousseau A, Garcion E*, Dumas F*. Harnessing Argonaute 2 as an Innovative Delivery System for siRNA in Glioblastoma. Journal of Drug Delivery Science and Technology, 114 (2025) 107459. *Equivalent contributions. DOI: 10.1016/j.jddst.2025.107459.

Clavreul A, Guillonneau F, Blanchet O, Lasla H, Rousseau A, Guette C, Boissard A, Henry C, Dhondt M, Jézéquel P, Menei P, Lemée. JM. A DIA-MS-based proteomics approach to find potential serum prognostic biomarkers in glioblastoma patients. Molecular Oncology, 19(9) (2025) 2686-2699. doi: 10.1002/1878-0261.70068.

Gonzalez-Prada I, Barcelos A, Dion M, Magariños B, Lapoujade C, Rousseau A, Concheiro A, Garcion E*, Alvarez-Lorenzo C*. Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment. Journal of Controlled Release, 381 (2025) 113615. *Equivalent contributions. DOI: 10.1016/j.jconrel.2025.113615.

Roncali L, Marionneau-Lambot S, Roy C, Eychenne R, Gouard S, Avril S, Chouin N, Riou J, Allard M, Rousseau A, Guérard F, Hindré F, Chérel M*, Garcion E*. Brain intratumoral astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice. eBiomedicine, the Lancet discovery science, 105 (2024) 105202. *Equivalent contributions. DOI: 10.1016/j.ebiom.2024.105202.

Sourty B, Basset L, Fontaine A, Garcion E, Rousseau A. Chromothripsis is rare in IDH-mutant gliomas compared to IDH-wildtype glioblastomas whereas whole-genome duplication is equally frequent in both tumor types. Neuro-Oncology Advances, 6(1) (2024) vdae059. DOI: 10.1093/noajnl/vdae059.

Rinaldi A., Dumas F., Duskey J.T., Imbriano C., Belluti S., Roy C., Ottonelli I., Vandellia M.A., Ruozi B., Garcion E., Tosi G., Boury F. Polymer-lipid Hybrid Nanomedicines to Deliver siRNA in and Against Glioblastoma Cells. International Journal of Pharmaceutics, 654 (2024) 123994. DOI: 10.1016/j.ijpharm.2024.123994.

Molina-Peña R^#, Ferreira NH^#, Roy C, Roncali L, Najberg M, Avril S, Zarur M, Bourgeois W, Ferreirós A, Lucchi C, Cavallieri F, Hindré F, Tosi G, Biagini G, Valzania F, Berger F, Abal M, Rousseau A, Boury F, Alvarez-Lorenzo C*, Garcion E*. Implantable SDF-1α-loaded silk fibroin hyaluronic acid aerogel sponges as an instructive component of the glioblastoma ecosystem: Between chemoattraction and tumor shaping into resection cavities. Acta Biomaterialia, 173 (2024) 261–282. ^#,*Equivalent contributions. DOI: 10.1016/j.actbio.2023.10.022.

Simion V, Loussouarn C, Laurent C, Roncali L, Gosset D, Reverchon F, Rousseau A, Martin F, Midoux P, Pichon C, Garcion E*, Baril P*. LentiRILES, a miRNA-ON Sensor System for Monitoring the Functionality of miRNA in Cancer Biology and Therapy. RNA Biology, 8, NO. S1 (2021) 198–214. *Equivalent contributions. DOI: 10.1080/15476286.2021.1978202.

Najberg M, Haji Mansor M, Taillé T, Bouré C, Molina-Pena R, Boury F, Cenis JL, Garcion E*, Alvarez-Lorenzo C*. Aerogel sponges of silk fibroin, hyaluronic acid and heparin for soft tissue engineering: composition-properties relationship. Carbohydrate Polymers, 237 (2020) 116107. *Equivalent contributions. DOI: 10.1016/j.carbpol.2020.116107.

Download PDF "List of team member publications"

HORIZON-TMA-MSCA-DN InnovaRTBRAIN “Innovative Radiation Therapy for brain tumors” (Proposal number: 101311303).
Partner – E. Garcion – Evaluation score: 96%.
4,194 k€ total and €315 k€ for the team (2026-2030)

INSERM PCSI GLIOGEL "Smart hyperbranched cationic polymers to deliver siRNA and complementary therapeutics using a lipid nanoparticles-based hydrogel implant after glioblastoma post-resection."
Partner – E. Garcion – 3 French partners
659 k€ total and 238 f€ for the team (2026-2029)

PHRC-K INCa STRONG "SupraTotal Resection Of Newly diagnosed Glioblastomas: impact on survival and quality of life" (PHRC-K26-221).
Coordinator – JM Lemée – 22 recruitment centers
807 k€ total – Managed by CHU d'Angers, DRCI.

EuroNanoMed-III GLIOSILK “Silk-fibroin Interventional Nano-trap for Glioblastoma” (ERA-NET (European Research Area Network) COFUND, ANR-19-ENM3-0003-01).
Coordinator – E Garcion – 4 European partners France, Spain, Italy, 1 SME.
830 k€ and 148 k€ for the team (2020-2023)

Bilateral International Agreements
PI – F Boury – 2 partners each
475 k€ total and 237,5 k€ (2023-2026)

PhD Co-supervision with the University of Modena - Italy (UNIMORE) - appointment of Visiting Professor "Advanced nanotechnologies for the central nervous system: design, optimization, application, and scale-up" 160 k€ total and 80 k€ for the team (2020-2022)
Bioregate SPEEBO - CERM of Liège (Belgium): "Bioactive scaffolds from pickering emulsions for enhanced bone osteogenesis" 75 k€ total and 37.5 k€ for the team (2022-2023)
PROTEA - Hubert Curien Franco-South African Partnership (Western Cape University - UWC): "Effective drug-particle treatment of Tuberculosis" 20 k€ total and 10 k€ for the team (2020-2025)
VINCI Franco-Italian University (UNIMORE): "Innovative Technological approaches for targeting glioblastoma" (2020-2023) 200 k€ total and 100 k€ for the team (2020-2023)
ECOS SUD Program Argentina (Universidad Nacional de La Plata – UNLP:) GLIOCELL "Design of nanocomposite hydrogels for locoregional treatment of glioblastoma" 20 k€ total and 10 k€ (2023-2026)

LABEX IRON “Innovative Radiopharmaceuticals in Neurology & Oncology” (ANR-11-LABX-18-01)
Coordinator – F Kraeber-Bodéré (Nantes) – 11 teams
Scientific coordination of the translational project TP6 “Tumor response after radionuclide therapy” – E Garcion
1.8 M€ and 124 k€ for the team (2020-2024)

LABEX DHOLMEN - NEXT NU “Development in Hemato-OncoLogy and precision nuclear
MEdiciNe” - Contribution to WP “Innovative targeted radiotherapy in refractory solid tumors” – E Garcion
1.7 M€ and 60 k€ for the team (2025-2029)

Ligue Nationale contre le Cancer - National AAP Therapeutic RNA - FusTarG “Design and application of precision RNA oligonucleotides and aptamers for targeting gene fusion products in glioblastoma”.
Coordinator – E Garcion (with A Rousseau as co-PI) – partnership with Pasteur Institute
331 k€ and 181 k€ for the team (2023-2026)

INCa - Integrated Research Action Program (PAIR brain tumors) - ACT4GBM “Targeting Glioblastomas through Adoptive Transfer of Vy9V82 T Lymphocytes Expressing OAcGD2-CAR“.
Coordinator – C Pecqueur (Nantes) – 5 teams
Team 5 PI – P Menei (with A Clavreul as co-PI)
544 k€ and 98 k€ for the team (2022-2025)

Cancéropôle Grand-Ouest - Federative Project Target’IN “Improvement of Targeting Radiopharmaceuticals for Better Diagnostic and Therapy in Nuclear Medicine”
Coordinator – R Tripier (Brest) – 5 partners
PI – E Garcion (with F Hindré as co-PI)
280 k€ and 48 k€ for the team (2024-2026)

Cancéropôle Grand-Ouest - Emergence Call GRIP M3DS “PTN implants & glioblastoma recurrence”
PI – F Dumas – 2 partners
30 k€ and 15 k€ for the team (2026-2027)

PhD Pays de la Loire Region (PDL)
123 k€ for the team (2024-2027) + 123 k€ shared (2025-2028)

INSERM-PDL: “Immunostimulatory Interventional Implants” PI – E Garcion & F Dumas (2024-2027)
GIP ARRONAX-PDL: “Radiolabeled aptamers & glioblastoma treatment” Inserm Transfert consortium between CRCI2NA – Arronax – Pasteur Institute PI – E Garcion (2025-2028)

PhD Ministry of Higher Education and Research (MESRI) & UA
360 k€ for the team (2024-2027)

MESRI & UA 1: “Development and evaluation of bioimplants as cancer cell traps for glioblastoma treatment” PI – F. Boury & E Garcion (2020-2023)
MESRI & UA 2: “Caractérisation et ciblage par ARN interférence d’un gène de fusion dans le glioblastome” PI – A. Rousseau & E Garcion (2022-25)
MESRI & UA 3: “locoregional delivery system for STING agonists and siRNA in glioblastoma” PI – F. Boury & F Dumas (2025-2028)

Recurring funding for the team:

CRCI2NA-Inserm: 88 k€ in 4 years (ongoing contract)
University of Angers: 150 k€ in 4 years (ongoing contract)

Patient Association Donations: from ARTC administrator “Locoregional Sting pathway stimulation” to E Garcion & from Des Etoiles dans la Mer “Replace the brain biopsy with a blood sample” to A Clavreul
40.7 k€ (2025-2027)

High-impact and internationally visible publications
Findings published in leading international journals, including eBioMedicine (The Lancet Discovery Science), Theranostics, J Control. Rel., Acta Biomat. & Mol. Oncol., on innovative locoregional and targeted therapies for glioblastoma. The team's results span fundamental biology, technology and radiopharmaceutical sciences, including innovative nanoparticles, RNA-based nanomedicines, tumor-trapping bioimplants and the identification of clinically relevant genetic fusions.

Competitive funding and project leadership
Over the last five years, the team has secured >2.5 M€ in national and international competitive funding, with multiple projects coordinated by team members (HORIZON MSCA DN InnovaRTbrain, PCSI Inserm Gliogel, EuroNanoMed III Gliosilk (ANR-19-ENM3-0003-01), INCa PHRC-K Strong (PHRC-K26-221), INCa PAIR Brain Tumors ACT4GBM, Labex IRON ANR-11-LABX-18-01, Ligue Nationale contre le Cancer "Therapeutic RNAs" FustTarg, Labex DHOLMEN, Region PDL).

Expertise at the interface of innovation and clinical translation
GLIAD has developed expertise in molecular, nano-, and radiopharmaceutical-based locoregional therapies, including targeted internal radiotherapy and implantable therapeutic devices. This is supported by preclinical validation, close clinician involvement, and active preparation for early-phase or phase III clinical trials (PHRC-K), connecting preclinical innovation with patient-oriented research.

International strategy and networks
GLIAD is involved in, and has led, international programs and consortia, including EuroNanoMed III Gliosilk, HORIZON MSCA DN InnovaRTbrain, Erasmus Mundus NanoFar, VINCI, ECOS, PROTEA, with long-term collaborations with academic, clinical and industrial partners across Europe and beyond.

Training and mentorship
From 2020 to 2026, the team has trained 13 PhD graduates and currently supervises 6 ongoing theses. With 7 HDR-qualified members, international supervision, and leadership of joint doctoral and double-degree programs, GLIAD contributes to training the next generation of researchers in innovative anticancer therapies.

Scientific visibility, leadership and recognition.
GLIAD PIs hold leadership positions in national and international scientific and expert networks as well as research infrastructures. A. Rousseau is President of the French Society of Neuropathology, Editor-in-Chief of Annales de Pathologie, and plays major roles in the INCa-supported RENOCLIP network and in national neuro-oncology initiatives including ANOCEF. JM. Lemée coordinates the Neuro-Oncology Group of the French Society of Neurosurgery (SFNC), serves as Editor of Neurochirurgie, and contributes to national neuro-oncology programmes including the French GBM Biobank (BCB; DC-2011-1467, AC-2023-5473) and the TANGO study (NCT04288505). F. Lacoeuille leads the radiopharmaceutical working group of the French Society of Nuclear Medicine (SFMN), served on the Scientific Council of the Ligue Nationale contre le Cancer (2022–2025), and serves on editorial boards and multicentre clinical trials (PASSIFLORE, ICO; PENTILULA, CHU Nantes). E. Garcion is a European expert for EuroNanoMed/ERA4Health, editorial board member (Transl. Oncol., Front. Pharmacol.), and reviewer for leading journals (Nat. Commun., J. Control. Release, etc.); he coordinated the EuroNanoMed III GLIOSILK project, and leads the ongoing LNCC FusTarG consortium, as well as supervising the Platform for Cellular and Molecular Analysis (PACeM). F. Hindré directs the PRIMEX radiobiology and experimental imaging platform and coordinated the 2025 acquisition of a nano-SPECT/PET/CT system for preclinical theranostics in Angers F. Boury is a member of the Scientific Advisory Board of Biogenouest and has contributed to the development of international collaborations through bilateral programmes with South Africa (PROTEA), Argentina (ECOS-Sud) and Italy (VINCI). Team members contribute to major European and national initiatives including LabEx IRON & NExT DHOLMEN, INCa PAIR ACT4GBM and Horizon Europe MSCA DN InnovaRTBrain, and play an active role in the Imaging and Radiotherapy network of Cancéropôle Grand Ouest through federative (Target'IN) and emerging projects (GRIPM3DS, F. Dumas). The team also contributes to the organization of international meetings (NTHS, C'Nano, DIU Neuro-Oncol., CRCI2NA Symposium, VIR-CGO workshops, Gen2Bio), reinforcing GLIAD's visibility in neuro-oncology, nanomedicine and radiopharmaceutical sciences.

International

Carmen Alvarez-Lorenzo & Barbara Blanco Fernandez, FIDIS - IDIS - University of Santiago de Compostela (USC), Spain.
=> Advanced biomaterials and nanocarriers for locoregional drug delivery; biofabrication to optimize targeted therapies and preclinical testing.

Christine Jérôme & Antoine Debuigne, Center for Education and Research on Macromolecules (CERM), University of Liège, Belgium.
=> Innovative polymers, smart biomaterials & nanomaterials.

Roland Hustinx, Bernard Rogister & Virginie Neirinckx, CHU-Liège and GIGA-Neurosciences, Université de Liège, Belgium.
=> Developing & validating new radiopharmaceuticals for diagnosis & therapy; implementing advanced imaging technologies, AI, reconstruction & dosimetry.

Yolanda Prezado, CiMUS, New Approaches in Radiotherapy, USC, Spain.
=> Radiobiology, innovative therapies and therapeutic combinations.

Dea Slade, Dea Slade, Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria.
=> Developing and deciphering intrinsic tumor cell responses to vectorized radiotherapy in glioblastoma through omics approaches.

Admire Dube, School of Pharmacy, University of the Western Cape (UWC), Cape Town, South Africa.
=> Drug-particle delivery & treatment

German Islan, Centro de Investigación y Desarrollo en Fermentaciones Industriales y Biotecnología Aplicada (CINDEFI), Universidad Nacional de La Plata (UNLP), La Plata, Argentina.
=> Drug-interventionnal implant delivery & treatment

France

Marcel Hollenstein, Pasteur Institute, Bioorganic chemistry of nucleic acids, Paris, France.
=> Developing and deciphering the role of new aptamers and ODN in glioblastoma.

Férid Haddad, Aurélien Vidal, GIP Arronax, Saint-Herblain, France
=> Developing and deciphering functions of new radiopharmaceuticals against glioblastoma.

Patrick Baril, Centre de Biophysique Moléculaire (CBM), CNRS, Orléans, France.
=> Developing and deciphering innovative RNAi targeting and subcellular routing in glioblastoma.

Elodie Segura, Institut Necker Enfants Malades (INEM), INSERM U1151, Paris, France.
=> Developing and deciphering the role of immunity and the tumor microenvironment in the response to vectorized radiotherapy in glioblastoma.

Guillaume Bastiat, Mint, Angers, France
=> Interventional implants and RNAi targeting in glioblastoma.

Sagrario Pascual, IMMM – Institut des Molécules et Matériaux du Mans, Le Mans, France.
=> Innovative polymers and interventional implants in glioblastoma.

VIR Network: https://www.canceropole-grandouest.com/les-reseaux-cgo/vectorisation-imagerie-radiotherapies/

Partnerships with industries (valorization) and/or clinical services

NasasBiotech SL:
=> Consortium agreement Inserm Transfert
=> Brain tumor targeted interventionnal implants

HTL Biotechnology:
=> Consortium agreement Inserm Transfert
=> Brain tumor targeted interventionnal implants

TargTex SA:
=> Establishing a collaboration
=> Targeted delivery for hard-to-treat brain cancers

Pasteur Institute (private foundation recognized as being of public utility):
=> Consortium agreement Inserm Transfert
=> Aptamers and ASOs targeting brain tumors

Department of Nuclear Medicine & Department of Neurosurgery of the Angers University hospital (CHU):
=> Approved for Phase I clinical trials
=> Involve GLIAD team members
=> Work in close synergy with the house research center