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

Michael Roth, David M. Barris, Sajida Piperdi, Vicky Kuo, Stephanie Everts, David S. Geller, Peter Houghton, E. Anders Kolb, Thomas Hawthorne, Jonathan Gill, Richard Gorlick

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)32-38
Number of pages7
JournalPediatric Blood and Cancer
Volume63
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Osteosarcoma
Glycoproteins
Antibodies
Pharmaceutical Preparations
Therapeutics
Cell Line
Membrane Glycoproteins
glembatumumab vedotin
Immunohistochemistry
Messenger RNA
Young Adult
Melanoma
Flow Cytometry
Proteins
Enzyme-Linked Immunosorbent Assay
Clinical Trials
Breast Neoplasms

Keywords

  • Antibody-drug conjugate
  • Glembatumumab vedotin
  • GPNMB
  • Osteosarcoma

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma. / Roth, Michael; Barris, David M.; Piperdi, Sajida; Kuo, Vicky; Everts, Stephanie; Geller, David S.; Houghton, Peter; Kolb, E. Anders; Hawthorne, Thomas; Gill, Jonathan; Gorlick, Richard.

In: Pediatric Blood and Cancer, Vol. 63, No. 1, 01.01.2016, p. 32-38.

Research output: Contribution to journalArticle

Roth, M, Barris, DM, Piperdi, S, Kuo, V, Everts, S, Geller, DS, Houghton, P, Kolb, EA, Hawthorne, T, Gill, J & Gorlick, R 2016, 'Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma', Pediatric Blood and Cancer, vol. 63, no. 1, pp. 32-38. https://doi.org/10.1002/pbc.25688
Roth, Michael ; Barris, David M. ; Piperdi, Sajida ; Kuo, Vicky ; Everts, Stephanie ; Geller, David S. ; Houghton, Peter ; Kolb, E. Anders ; Hawthorne, Thomas ; Gill, Jonathan ; Gorlick, Richard. / Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma. In: Pediatric Blood and Cancer. 2016 ; Vol. 63, No. 1. pp. 32-38.
@article{22cb12e890d849b999ee902b2b98ebe2,
title = "Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma",
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 = "Antibody-drug conjugate, Glembatumumab vedotin, GPNMB, Osteosarcoma",
author = "Michael Roth and Barris, {David M.} and Sajida Piperdi and Vicky Kuo and Stephanie Everts and Geller, {David S.} and Peter Houghton and Kolb, {E. Anders} and Thomas Hawthorne and Jonathan Gill and Richard Gorlick",
year = "2016",
month = "1",
day = "1",
doi = "10.1002/pbc.25688",
language = "English (US)",
volume = "63",
pages = "32--38",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma

AU - Roth, Michael

AU - Barris, David M.

AU - Piperdi, Sajida

AU - Kuo, Vicky

AU - Everts, Stephanie

AU - Geller, David S.

AU - Houghton, Peter

AU - Kolb, E. Anders

AU - Hawthorne, Thomas

AU - Gill, Jonathan

AU - Gorlick, Richard

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Antibody-drug conjugate

KW - Glembatumumab vedotin

KW - GPNMB

KW - Osteosarcoma

UR - http://www.scopus.com/inward/record.url?scp=84951173947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84951173947&partnerID=8YFLogxK

U2 - 10.1002/pbc.25688

DO - 10.1002/pbc.25688

M3 - Article

VL - 63

SP - 32

EP - 38

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

IS - 1

ER -