Dinutuximab (Unituxin), also known as ch14.18 (United Therapeutics Corporation [UTC]), is a novel chimeric, human-murine, anti-GD2 monoclonal antibody that underwent priority review by the Food and Drug Administration (FDA) and received approval with an orphan drug designation on March 10, 2015. It is the first monoclonal antibody specifically approved for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin (13-cis-retinoic acid [RA]) for the maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy.
Tumor-associated gangliosides have emerged as promising targets for the development of monoclonal antibodies as immunotherapy for treating various cancers. Gangliosides (eg, GD2, GM2, GD3, NGcGM3, and OAcGD2) are glycosylated lipid molecules that belong to the glycosphingolipid class. GD2 is unique in that it is found in low levels on the surface of neurons, skin melanocytes, and peripheral sensory nerve fibers but is highly expressed on the cell surface of neuroblastomas. It has also been detected in melanomas, bone and soft-tissue sarcomas, and small-cell lung cancer. GD2 signaling has been shown to result in tumor growth and metastasis.
Dinutuximab binds to surface GD2 and signals antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which results in tumor regression. Patients with high-risk neuroblastoma receive intense chemotherapy and undergo stem cell transplantation resulting in an immunosuppressed state. Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-2 (IL-2) increase production and activation of natural killer T cells, macrophages, and neutrophils from the patient’s own immune system to further enhance cytotoxicity against the neuroblastoma. Thus, dinutuximab is approved for administration with GM-CSF and IL-2.
Fig.1 Mechanism of Action of Dinutuximab
Table 1. Clinical Projects of Dinutuximab*
Table 2. Approved Drugs of Dinutuximab**
* The table was excerpted from the following website
** Information presented in the table were collected from the following website: