From netrin‐1‐targeted SPECT / CT to internal radiotherapy for management of advanced solid tumors
| العنوان: | From netrin‐1‐targeted |
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| المؤلفون: | David Kryza, Jennifer Wischhusen, Mathieu Richaud, Maëva Hervieu, Jacqueline Sidi Boumedine, Jean‐Guy Delcros, Sophie Besse, Thomas Baudier, Pierre‐Alexandre Laval, Silvia Breusa, Erwan Boutault, Hugo Clermidy, Nicolas Rama, Benjamin Ducarouge, Mojgan Devouassoux‐Shisheboran, Jean‐Michel Chezal, Anne‐Laure Giraudet, Thomas Walter, Patrick Mehlen, David Sarrut, Benjamin Gibert |
| المساهمون: | Laboratoire d'automatique, de génie des procédés et de génie pharmaceutique (LAGEPP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne (UCA), Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Netris Pharma, Partenaires INRAE, Hospices Civils de Lyon (HCL) |
| المصدر: | EMBO Molecular Medicine EMBO Molecular Medicine, 2023, 15, ⟨10.15252/emmm.202216732⟩ |
| بيانات النشر: | HAL CCSD, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | netrin, cancer extracellular matrix netrin radioimmunotherapy targeted therapy Subject Categories Cancer Pharmacology & Drug Discovery, extracellular matrix, radioimmunotherapy, Molecular Medicine, cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacology & Drug Discovery, targeted therapy |
| الوصف: | International audience; Targeted radionuclide therapy is a revolutionary tool for the treatment of highly spread metastatic cancers. Most current approaches rely on the use of vectors to deliver radionuclides to tumor cells, targeting membrane-bound cancer-specific moieties. Here, we report the embryonic navigation cue netrin-1 as an unanticipated target for vectorized radiotherapy. While netrin-1, known to be reexpressed in tumoral cells to promote cancer progression, is usually characterized as a diffusible ligand, we demonstrate here that netrin-1 is actually poorly diffusible and bound to the extracellular matrix. A therapeutic anti-netrin-1 monoclonal antibody (NP137) has been preclinically developed and was tested in various clinical trials showing an excellent safety profile. In order to provide a companion test detecting netrin-1 in solid tumors and allowing the selection of therapy-eligible patients, we used the clinical-grade NP137 agent and developed an indium-111-NODAGA-NP137 single photon emission computed tomography (SPECT) contrast agent. NP137-111 In provided specific detection of netrin-1-positive tumors with an excellent signal-to-noise ratio using SPECT/CT imaging in different mouse models. The high specificity and strong affinity of NP137 paved the way for the generation of lutetium-177-DOTA-NP137, a novel vectorized radiotherapy, which specifically accumulated in netrin-1-positive tumors. We demonstrate here, using tumor cell-engrafted mouse models and a genetically engineered mouse model, that a single systemic injection of NP137-177 Lu provides important antitumor effects and prolonged mouse survival. Together, these data support the view that NP137-111 In and NP137-177 Lu may represent original and unexplored imaging and therapeutic tools against advanced solid cancers. |
| اللغة: | English |
| تدمد: | 1757-4676 1757-4684 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a9bcbf1f2752c2a6e92c99edabd903cTest https://cnrs.hal.science/hal-04107206Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4a9bcbf1f2752c2a6e92c99edabd903c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17574676 17574684 |
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