Copper chelation redirects neutrophil function to enhance anti-GD2 antibody therapy in neuroblastoma
Year: 2024
Type: article
Abstract: Anti-disialoganglioside (GD2) antibody therapy has provided clinical benefit to patients with neuroblastoma however efficacy is likely impaired by the immunosuppressive tumor microenvironment. We have previously defined a link between intratumoral copper levels and immune evasion. Here, we report that adjuvant copper chelation potentiates anti-GD2 antibody therapy to confer durable tumor control in immunocompetent models of neuroblastoma. Mechanistic studies reveal copper chelation creates an immune-primed tumor microenvironment through enhanced infiltration and activity of Fc-receptor-bearing cells, specifically neutrophils which are emerging as key effectors of antibody therapy. Moreover, we report copper sequestration by neuroblastoma attenuates neutrophil function which can be successfully reversed using copper chelation to increase pro-inflammatory effector functions. Importantly, we repurpose the clinically approved copper chelating agent Cuprior as a non-toxic, efficacious immunomodulatory strategy. Collectively, our findings provide evidence for the clinical testing of Cuprior as an adjuvant to enhance the activity of anti-GD2 antibody therapy and improve outcomes for patients with neuroblastoma.
Source: Nature Communications
Authors: Jourdin R. C. Rouaen, Antonietta Salerno, Tyler Shai-Hee, Jayne E. Murray, Giulia Castrogiovanni, Charlotte McHenry, Toni Rose Jue, Vu Pham, Jessica Lilian Bell, Ensieh Poursani, Emanuele Valli, Riccardo Cazzoli, Naomi Damstra, Delia J. Nelson, Kofi L. P. Stevens, Jonathan Chee, Iveta Slapetova, Maria Kasherman, Renee Whan, Francis Lin, Blake J. Cochran, Nicodemus Tedla, Feyza Colakoglu Veli, Aysen Yuksel, Chelsea Mayoh, Federica Saletta, Daniele Mercatelli, Tatyana Chtanova, Arutha Kulasinghe, Daniel Catchpoole, Giuseppe Cirillo, Maté Biro, Holger N. Lode, Fabio Luciani, Michelle Haber, Juliet C. Gray, Toby N. Trahair, Orazio Vittorio
Institutions: UNSW Sydney, European Institute of Oncology, The University of Western Australia, Curtin University, Institute for Respiratory Health, EMBL Australia, Children's Hospital at Westmead, University of Bologna, Garvan Institute of Medical Research, The University of Queensland, University of Calabria, Universitätsmedizin Greifswald, Universität Greifswald, Kirby Institute, University of Southampton, Sydney Children's Hospital
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
OpenAlex ID: W4405329789