Targeting and killing glioblastoma with monoclonal antibody to O-acetyl GD2 ganglioside

Abstract

There are still unmet medical needs in the treatment of glioblastoma, the most common and the most aggressive glioma of all brain tumors. Here, we found that O-acetyl GD2 is expressed in surgically resected human glioblastoma tissue. In addition, we demonstrated that 8B6 monoclonal antibody specific for O-acetylat GD2 could effectively inhibit glioblastoma cell proliferation in vitro and in vivo. Taken together, these results indicate that O-acetylated GD2 represents a novel antigen for immunotherapeutic-based treatment of high-grade gliomas.

TargetingO-Acetyl-GD2 Ganglioside for Cancer Immunotherapy

“…Taken together, these data suggest that GD2 is differentially acetylated in normal and tumor tissue and that normal tissues expressing GD2 may not express O- acetyl-GD2. This prompted us to investigate the expression of O -acetyl-GD2 in glioblastoma multiforme (GBM) [87], a cancer that is known to express GD2 [20]. We confirmed the presence of O -acetyl-GD2 on GBM biopsies obtained after surgical resection.…”

“…We confirmed the presence of O -acetyl-GD2 on GBM biopsies obtained after surgical resection. We also demonstrated high O -acetyl-GD2 expression on GBM cell lines and patient-derived tumor cells [87]. Of note, GBM is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations, including glioblastoma stem cells (GSCs) [88].…”

“…However, ADCC is considered as an important clinical mechanism for anti-GD2 immunotherapy [102, 103]. In this respect, anti- O -acetyl-GD2 mAbs seem to be particularly effective as compared to anti-GD2 antibodies in mediating ADCC against O -acetyl-GD2-expressing tumor cells [39, 87, 104]. We also found that anti- O -acetyl-GD2 mAb antibodies induce significant CDC in addition to ADCC in vitro [39].…”

Impairing temozolomide resistance driven by glioma stem‐like cells with adjuvant immunotherapy targeting O‐acetyl GD2 ganglioside

“…We have previously identified O‐acetyl derivative of GD2 ganglioside, namely, O‐acetyl‐GD2 (OAcGD2), as a new target antigen for GBM immunotherapy with monoclonal antibodies (mAbs) . The mechanisms by which anti‐OAcGD2 mAbs induce GBM tumor cell killing involve antibody‐dependent cell cytotoxicity and induction of cell death with features of oncosis . Moreover, OAcGD2 expression prevails post immunotherapy in vivo , suggesting the absence of an immunoediting process that would select OAcGD2‐negative tumor cells .…”

Anti-GD2-ch14.18/CHO coated nanoparticles mediate glioblastoma (GBM)-specific delivery of the aromatase inhibitor, Letrozole, reducing proliferation, migration and chemoresistance in patient-derived GBM tumor cells

“…Disialogangliosidase2 (GD2) is a highly glycosylated sphingolipid which has been shown to be highly expressed in high-grade gliomas [16] in addition to several other cancer types [17]. It was also reported as a target for glioblastoma [18] but, to date, there has been no clinical development related to GBM. Clinical experience with anti-GD2 antibodies was generated in neuroblastoma, a paediatric malignancy characterized by high GD2 expression.…”