Dinutuximab Overview

Introduction of Dinutuximab

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.

Mechanism of Action of Dinutuximab

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.

Mechanism of Action of Dinutuximab Fig.1 Mechanism of Action of Dinutuximab

Table 1. Clinical Projects of Dinutuximab*

NCT ID Status Conditions Lead Sponsor Update Time
NCT03098030 Active, not recruiting Small Cell Lung Cancer United Therapeutics March 31, 2017
NCT02169609 Active, not recruiting Neuroblastoma, Neoplasm Residual, Effects of Immunotherapy Fundació Sant Joan de Déu June 23, 2014
NCT03332667 Recruiting Neuroblastoma New Approaches to Neuroblastoma Therapy Consortium November 6, 2017
NCT03786783 Recruiting Ganglioneuroblastoma, High-Risk Neuroblastoma National Cancer Institute (NCI) December 26, 2018
NCT02484443 Active, not recruiting Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Recurrent Osteosarcoma National Cancer Institute (NCI) June 29, 2015
NCT04211675 Not yet recruiting Relapsed Neuroblastoma, Refractory Neuroblastoma Nationwide Children's Hospital December 26, 2019
NCT04253015 Active, not recruiting Neuroblastoma EusaPharma (UK) Limited February 5, 2020
NCT03794349 Recruiting Ganglioneuroblastoma, Recurrent Neuroblastoma, Refractory Neuroblastoma Children's Oncology Group January 7, 2019
NCT01711554 Active, not recruiting Recurrent Neuroblastoma, Refractory Neuroblastoma National Cancer Institute (NCI) October 22, 2012
NCT02743429 Recruiting Neuroblastoma University Medicine Greifswald April 19, 2016
NCT02573896 Recruiting Neuroblastoma New Approaches to Neuroblastoma Therapy Consortium October 12, 2015
NCT02914405 Recruiting Neuroblastoma University Hospital Southampton NHS Foundation Trust September 26, 2016

Table 2. Approved Drugs of Dinutuximab**

INN (trade name) Therapeutic area Dose Strength Route Company Marketing start Market
Unituxin Neuroblastoma Solution 3.5 mg / mL Intravenous UNITED THERAP March 10, 2015
Unituxin Neuroblastoma Solution 3.5 mg / mL Intravenous United Therapeutics Europe Ltd August 14, 2015
Unituxin Neuroblastoma Solution 3.5 mg / mL Intravenous United Therapeutics Corporation May 1, 2019

What We Provide

Therapeutic Antibody

We provide high-quality (IgG1κ type) for immunoassay techniques such as: Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Immunofluorescence; Immunoprecipitation; Flow Cytometry; Functional Studies. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

References
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Dinutuximab
** Information presented in the table were collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125516
https://www.ema.europa.eu/en/medicines/human/EPAR/unituxin
https://health-products.canada.ca/dpd-bdpp/dispatch-repartition.do;jsessionid=E601E63913E00987ED0F9ADAD666968A


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