Anti-CCL2 antibody combined with etoposide prolongs survival in a minimal residual disease mouse model of neuroblastoma

Danny Lascano; Michael J Zobel; William G Lee; Stephanie Y Chen; Abigail Zamora; Grace E Asuelime; So Yung Choi; Antonios Chronopoulos; Shahab Asgharzadeh; Araz Marachelian; Jinseok Park; Michael A Sheard; Eugene S Kim

doi:10.1038/s41598-023-46968-2

Anti-CCL2 antibody combined with etoposide prolongs survival in a minimal residual disease mouse model of neuroblastoma

Sci Rep. 2023 Nov 14;13(1):19915. doi: 10.1038/s41598-023-46968-2.

Authors

Danny Lascano^#¹, Michael J Zobel^#¹, William G Lee¹, Stephanie Y Chen¹, Abigail Zamora¹, Grace E Asuelime¹, So Yung Choi², Antonios Chronopoulos³, Shahab Asgharzadeh^{3

4}, Araz Marachelian^{3

4}, Jinseok Park³, Michael A Sheard⁵, Eugene S Kim^{6

7

8

9}

Affiliations

¹ Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA.
² Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³ Division of Hematology, Oncology and Blood and Marrow Transplantation, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁵ The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁶ Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA. [email protected].
⁷ Division of Hematology, Oncology and Blood and Marrow Transplantation, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [email protected].
⁸ Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [email protected].
⁹ Department of Surgery, Cedars-Sinai Medical Center, 116 N. Robertson Blvd, Suite PACT 700, Los Angeles, CA, 90048, USA. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Chemokine CCL2
Chemokines
Etoposide / pharmacology
Etoposide / therapeutic use
Humans
Ligands
Mice
Mice, Inbred NOD
Neoplasm, Residual / drug therapy
Neuroblastoma* / pathology

Substances

Etoposide
Ligands
Chemokines
Chemokine CCL2
CCL2 protein, human