Titre :

Anti-OAcGD2 antibody in combination with ceramide kinase inhibitor mediates potent antitumor cytotoxicity against breast cancer and diffuse intrinsic pontine glioma cells

Auteur(s) :

Kasprowicz, Angelina [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Cavdarli, Sumeyye [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Delannoy, Philippe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Le Guezennec, X. [Auteur]
International Institute of Molecular and Cell Biology [Warsaw] [IIMCB]
Defebvre, Clemence [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Spriet, Corentin [Auteur]
Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41
Jonckheere, Nicolas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Le Doussal, J. M. [Auteur]
Krzewinski, Marie-Ange [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Mitra, Suman [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Meignan, Samuel [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Groux, Sophie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]

Titre de la revue :

Molecular and Cellular Biochemistry

Nom court de la revue :

Mol. Cell. Biochem.

Éditeur :

Springer Nature

Date de publication :

2024-11-18

ISSN :

0300-8177

Mot(s)-clé(s) en anglais :

O-acetyl-GD2
Ganglioside
Immunotherapy
Breast cancer
Pediactric glioma

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

O-acetylated GD2 (OAcGD2) is a cancer-related antigen that is currently being explored for therapeutic use. Exploring the intricate mechanisms behind OAcGD2 synthesis in cancer cells has long been a challenge. Leveraging ...
Lire la suite >O-acetylated GD2 (OAcGD2) is a cancer-related antigen that is currently being explored for therapeutic use. Exploring the intricate mechanisms behind OAcGD2 synthesis in cancer cells has long been a challenge. Leveraging state-of-the-art high-throughput RNAi screening and confocal imaging technologies, our study delves into the genetic network orchestrating OAcGD2 synthesis in breast cancer cells. By conducting a comprehensive siRNA screen targeting the OAcGD2 phosphatome/kinome, we identified 43 genetic modulators, with 25 downregulating and 18 upregulating OAcGD2 synthesis. Among these, our study focused on CERK, the gene-encoding ceramide kinase, a pivotal player in glycosphingolipid metabolism. Through meticulous experimentation utilizing anti-CERK inhibitor and siRNAs, we made a significant discovery: CERK inhibition robustly upregulates OAcGD2 in both neuroblastoma and breast cancer cells, concurrently dampening cell migration. Furthermore, our findings highlight an exciting prospect: augmenting the antibody-dependent cell cytotoxicity of the chimeric human/mouse anti-OAcGD2 IgG1 monoclonal antibody (c8B6 mAb) against breast cancer and diffuse intrinsic pontine glioma cell lines in combination with specific CERK inhibitors. These results underscore the pivotal role of CERK inhibition in bolstering OAcGD2 synthesis, thus, presenting a promising strategy to increase the efficacy of anti-OAcGD2-based immunotherapy in patients with neuroectodermal tumors. By shedding light on this intricate interplay, our study paves the way for innovative therapeutic strategies poised to revolutionize the treatment landscape for these aggressive malignancies.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille
CNRS
Inserm
Institut Pasteur de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172
• Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Date de dépôt :

2024-11-27T22:07:19Z
2025-01-15T09:22:10Z