From netrin-1-targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors.
cancer
extracellular matrix
netrin
radioimmunotherapy
targeted therapy
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
11 04 2023
11 04 2023
Historique:
revised:
08
02
2023
received:
06
09
2022
accepted:
10
02
2023
medline:
12
4
2023
pubmed:
7
3
2023
entrez:
6
3
2023
Statut:
ppublish
Résumé
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 re-expressed 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-
Identifiants
pubmed: 36876343
doi: 10.15252/emmm.202216732
pmc: PMC10086585
doi:
Substances chimiques
Netrin-1
158651-98-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16732Subventions
Organisme : Agence Nationale de la Recherche (ANR)
Organisme : Cancéropole Clara (Oncostarter/PDC)
Organisme : Institut Convergence
Organisme : Institut National Du Cancer (INCa)
Organisme : La ligue contre le Cancer
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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