Ganglioside GD2 as a therapeutic target for antibody-mediated therapy in patients with osteosarcoma

Authors

  • Michael Roth MD,

    1. Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
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  • Marissa Linkowski MD,

    1. Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
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  • John Tarim MD,

    1. Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
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  • Sajida Piperdi MD,

    1. Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
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  • Rebecca Sowers MD,

    1. Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
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  • David Geller MD,

    1. Department of Orthopedic Surgery, Montefiore Medical Center and the Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
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  • Jonathan Gill MD,

    1. Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
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  • Richard Gorlick MD

    Corresponding author
    1. Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
    2. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York
    • Corresponding author: Richard Gorlick, MD, Division of Pediatric Hematology/Oncology, The Children's Hospital at Montefiore, 3415 Bainbridge Ave, Rosenthal Pavilion, Rm 300, Bronx NY, 10467; Fax: (718) 920-6506; RGorlick@montefiore.org

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  • We would also like to thank the National Cancer Institute for generously donating the 14.GD2a antibody.

Abstract

BACKGROUND

Survival outcomes for patients with osteosarcoma have remained stagnant over the past 30 years. Targeting of ganglioside GD2, a glycosphingolipid on the cell surface of some tumors, with immunotherapy has resulted in improved outcomes for patients with neuroblastoma. In the current study, the expression pattern of GD2 was examined in osteosarcoma.

METHODS

Immunohistochemistry was performed on osteosarcoma samples from patients at the time of initial biopsy, definitive surgery, and disease recurrence. The intensity and location of staining were scored. Cell-based enzyme-linked immunoadsorbent assay was performed on osteosarcoma cell lines to quantitate the level of GD2 expression.

RESULTS

Forty-four osteosarcoma samples were evaluated by immunohistochemistry, including 8 samples from the initial biopsy, 28 samples from the definitive surgery, and 8 samples from the time of disease recurrence. GD2 was expressed on all 44 osteosarcoma samples. Osteosarcoma tissue obtained at the time of disease recurrence demonstrated a higher intensity of staining compared with samples obtained at initial biopsy and definitive surgery (P = .016). The majority of osteosarcoma cell lines expressed GD2 at higher levels than the neuroblastoma cell line BE(2)-C.

CONCLUSIONS

Ganglioside GD2 is highly expressed on osteosarcomas. Clinical trials are needed to assess the efficacy of targeting GD2 in patients with osteosarcoma. Cancer 2014;120:548–554. © 2013 American Cancer Society.

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