dinutuximab

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Ligands
dinutuximab

GtoPdb Ligand ID: 7979

Synonyms: APN-311 | Ch14.18 | MAb-14.18 | Unituxin®

dinutuximab is an approved drug (FDA (2015))

Comment: Dinutuximab is a chimeric mouse/human monoclonal antibody targeting ganglioside-GD2.
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record.
A patent search identifies US20140170155 [4] as the applicable patent. US20140170155 reveals APN311 as a formulation of the mouse-human chimeric anti-GD2 antibody ch14.18 recombinantly produced in Chinese hamster ovary (CHO) cells. Efficacy of the preferred antibody was determined by its cytolysis capacity in GD2-expressing cells, as determined by a complement dependent cytolysis assay.

No information available.

No information available.

Summary of Clinical Use
In March 2015, the US FDA approved dinutuximab as a component of a multiagent, multimodality therapy (antibody + granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-2 (IL-2) + 13-cis-retinoic acid (isotretinoin)) for paediatric patients with high-risk neuroblastoma. In Europe, the antibody has been remanufactured (and referred to as dinutuximab beta or ch14.18/CHO) and is approved for use as Qarziba®. Qarziba can only be used in exceptional circumstances to treat neuroblastoma.

Summary of Clinical Use

In March 2015, the US FDA approved dinutuximab as a component of a multiagent, multimodality therapy (antibody + granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-2 (IL-2) + 13-cis-retinoic acid (isotretinoin)) for paediatric patients with high-risk neuroblastoma.
In Europe, the antibody has been remanufactured (and referred to as dinutuximab beta or ch14.18/CHO) and is approved for use as Qarziba®. Qarziba can only be used in exceptional circumstances to treat neuroblastoma.

Mechanism Of Action and Pharmacodynamic Effects
Ganglioside GD2 [2] is highly expressed on neuroectoderm-derived tumours and sarcomas, including neuroblastoma, retinoblastoma, melanoma and small cell lung cancer. In normal tissue GD2 expression is restricted to the brain making it inaccessible to circulating antibodies. This makes tumour GD2 an ideal target for immunotherapy [1]. Dinutuximab binds to GD2 and induces antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against GD2-expressing tumour cells [3].

Mechanism Of Action and Pharmacodynamic Effects

Ganglioside GD2 [2] is highly expressed on neuroectoderm-derived tumours and sarcomas, including neuroblastoma, retinoblastoma, melanoma and small cell lung cancer. In normal tissue GD2 expression is restricted to the brain making it inaccessible to circulating antibodies. This makes tumour GD2 an ideal target for immunotherapy [1]. Dinutuximab binds to GD2 and induces antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against GD2-expressing tumour cells [3].

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT04751383	Testing the Combination of Two Immunotherapy Drugs (Magrolimab and Dinutuximab) in Patients With Relapsed or Refractory Neuroblastoma or Relapsed Osteosarcoma	Phase 1 Interventional	National Cancer Institute (NCI)	This study will evaluate the combination of anti-CD47 () and anti-GD2 () antibodies in advanced solid tumour types.