Abstract

C–C motif chemokine ligand 2 (CCL2) is a monocyte chemoattractant that promotes metastatic disease and portends a poor prognosis in many cancers. To determine the potential of anti-CCL2 inhibition as a therapy for recurrent metastatic disease in neuroblastoma, a mouse model of minimal residual disease was utilized in which residual disease was treated with anti-CCL2 monoclonal antibody with etoposide. The effect of anti-CCL2 antibody on neuroblastoma cells was determined in vitro with cell proliferation, transwell migration, and 2-dimensional chemotaxis migration assays. The in vivo efficacy of anti-CCL2 antibody and etoposide against neuroblastoma was assessed following resection of primary tumors formed by two cell lines or a patient-derived xenograft (PDX) in immunodeficient NOD-scid gamma mice. In vitro, anti-CCL2 antibody did not affect cell proliferation but significantly inhibited neuroblastoma cell and monocyte migration towards an increasing CCL2 concentration gradient. Treatment of mice with anti-CCL2 antibody combined with etoposide significantly increased survival of mice after resection of primary tumors, compared to untreated mice.

Details

Title
Anti-CCL2 antibody combined with etoposide prolongs survival in a minimal residual disease mouse model of neuroblastoma
Author
Lascano, Danny 1 ; Zobel, Michael J. 1 ; Lee, William G. 1 ; Chen, Stephanie Y. 1 ; Zamora, Abigail 1 ; Asuelime, Grace E. 1 ; Choi, So Yung 2 ; Chronopoulos, Antonios 3 ; Asgharzadeh, Shahab 4 ; Marachelian, Araz 4 ; Park, Jinseok 3 ; Sheard, Michael A. 5 ; Kim, Eugene S. 6 

 Children’s Hospital Los Angeles, Division of Pediatric Surgery, Los Angeles, USA (GRID:grid.239546.f) (ISNI:0000 0001 2153 6013) 
 Cedars-Sinai Medical Center, Biostatistics and Bioinformatics Research Center, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905) 
 University of Southern California, Division of Hematology, Oncology and Blood and Marrow Transplantation, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
 University of Southern California, Division of Hematology, Oncology and Blood and Marrow Transplantation, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853); University of Southern California, Department of Pediatrics, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
 Children’s Hospital Los Angeles, The Saban Research Institute, Los Angeles, USA (GRID:grid.239546.f) (ISNI:0000 0001 2153 6013) 
 Children’s Hospital Los Angeles, Division of Pediatric Surgery, Los Angeles, USA (GRID:grid.239546.f) (ISNI:0000 0001 2153 6013); University of Southern California, Division of Hematology, Oncology and Blood and Marrow Transplantation, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853); University of Southern California, Department of Pediatrics, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853); Cedars-Sinai Medical Center, Department of Surgery, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905) 
Pages
19915
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2889800865
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.