2. Academic Validation
  3. Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma

Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma

  • Pediatr Blood Cancer. 2016 Jan;63(1):32-8. doi: 10.1002/pbc.25688.
Michael Roth 1,  David M Barris 1,  Sajida Piperdi 1,  Vicky Kuo 1,  Stephanie Everts 1,  David Geller 2,  Peter Houghton 3,  E Anders Kolb 4,  Thomas Hawthorne 5,  Jonathan Gill 1,  Richard Gorlick 1 6
Affiliations

Affiliations

  • 1 Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York.
  • 2 Department of Orthopaedic Surgery, Montefiore Medical Center and the Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York.
  • 3 Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas.
  • 4 Division of Pediatric Hematology/Oncology, A.I. duPont Hospital for Children, Wilmington, Delaware.
  • 5 Celldex Therapeutics, Branford, Connecticut.
  • 6 Department of Pediatrics and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York.
PMID: 26305408 DOI: 10.1002/pbc.25688
Abstract

Background: Cure rates for children and young adults with osteosarcoma have remained stagnant over the past three decades. Targeting glycoprotein non-metastatic b (GPNMB) with the antibody-drug conjugate glembatumumab vedotin has improved outcomes for patients with melanoma and breast Cancer. The potential utility of targeting GPNMB in osteosarcoma was explored.

Methods: GPNMB protein expression was evaluated by immunohistochemistry in human osteosarcoma tumor samples and by enzyme-linked immunosorbent assay (ELISA) in osteosarcoma cell lines. mRNA expression was measured by quantitative PCR in primary osteosarcoma samples and cell lines. Surface GPNMB expression was evaluated by flow cytometry and correlated with in vitro and in vivo cytotoxicity of glembatumumab vedotin.

Results: Sixty seven human osteosarcoma samples were evaluated by immunohistochemistry, including 12 samples from initial biopsy, 38 samples from definitive surgery, and 17 from the time of disease recurrence. GPNMB was expressed in 92.5% (62/67) of osteosarcoma samples. All primary osteosarcoma samples expressed high levels of GPNMB mRNA. Glembatumumab induced cytotoxic effects in 74% (14/19) of osteosarcoma cell lines, and GPNMB protein levels correlated with glembatumumab in vitro cytotoxicity (r = -0.46, P = 0.04). All osteosarcoma cell lines demonstrated surface GPNMB expression.

Conclusions: GPNMB is expressed in osteosarcoma and targeting GPNMB with the antibody-drug conjugate glembatumumab vedotin demonstrates osteosarcoma cytotoxic activity. Clinical trials are indicated to assess the efficacy of targeting GPNMB in patients with osteosarcoma.

Keywords

GPNMB; antibody-drug conjugate; glembatumumab vedotin; osteosarcoma.

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