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. 2014 Feb 15;120(4):548-54.
doi: 10.1002/cncr.28461. Epub 2013 Oct 25.

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

Michael Roth  1 , Marissa Linkowski, John Tarim, Sajida Piperdi, Rebecca Sowers, David Geller, Jonathan Gill, Richard Gorlick
Affiliations

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

Michael Roth et al. Cancer. .

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.

Keywords: antibody; ganglioside GD2; immunotherapy; osteosarcoma.

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Conflict of interest statement

The authors do not report any conflicts of interest.

Figures

Figure I
Figure I
Representative immunohistochemical staining for GD2 showing: (A) positive control (melanoma tissue stained with 14.G2a, (B) negative control (melanoma tissue stained with IgG2a isotype control, (C) positive (+++) osteosarcoma sample, (D) sporadic staining (+) osteosarcoma sample.
Figure I
Figure I
Representative immunohistochemical staining for GD2 showing: (A) positive control (melanoma tissue stained with 14.G2a, (B) negative control (melanoma tissue stained with IgG2a isotype control, (C) positive (+++) osteosarcoma sample, (D) sporadic staining (+) osteosarcoma sample.
Figure I
Figure I
Representative immunohistochemical staining for GD2 showing: (A) positive control (melanoma tissue stained with 14.G2a, (B) negative control (melanoma tissue stained with IgG2a isotype control, (C) positive (+++) osteosarcoma sample, (D) sporadic staining (+) osteosarcoma sample.
Figure I
Figure I
Representative immunohistochemical staining for GD2 showing: (A) positive control (melanoma tissue stained with 14.G2a, (B) negative control (melanoma tissue stained with IgG2a isotype control, (C) positive (+++) osteosarcoma sample, (D) sporadic staining (+) osteosarcoma sample.
FIGURE II
FIGURE II
GD2 expression in 24 osteosarcoma cell lines (c191-c323 and OS71). BE(2)-c (neuroblastoma cell line) and HT1080 (fibrosarcoma cell line) were used as controls. All 24 cell lines indicated the presence of GD2 cell-surface protein.
See this image and copyright information in PMC

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