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Th1226 details
Primary information
ID1837
ThPP IDTh1226
Therapeutic Peptide/Protein NameDinutuximab
SequenceNA view full sequnce in fasta
Functional ClassificationIIIc
Molecular Weight145000
Chemical FormulaC6422H9982N1722O2008S48
Isoelectric PointNA
HydrophobicityNA
Melting Point (℃)NA
Half LifeThe terminal half-life is 10 days
DescriptionDinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour. It is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse.
Indication/DiseaseDinutuximab is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse.
PharmacodynamicsIn vitro dinutuximab binds to neuroblastoma tumour cells and mediates the lysis of tumour cells via cell-mediated and complement-mediated cytotoxicity.
Mechanism of ActionDinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour.
ToxicityThe most common (incidence 15 %) grade 3 or 4 treatment-related adverse events in dinutuximab compared with standard therapy recipients were neuropathic pain (52 vs. 6 %), fever without neutropenia (39 vs. 6 %), any in-fection (39 vs. 22 %), hypokalaemia (35 vs. 2 %), hypersensitivity reactions (25 vs. 1 %), hyponatraemia (23 vs. 4 %), elevation of alanine transferase levels (23 vs. 3 %) and hypotension (18 vs. 0 %). Based on its mechanism of action, dinutuximab may cause fetal harm when administered to a pregnant woman however, there are no studies in pregnant women and no reproductive studies in animals to inform the drug-associated risk. Non-clinical studies suggest that dinutuximab-induced neuropathic pain is mediated by binding of the antibody to the GD2 antigen located on the surface of peripheral nerve fibers and myelin and subsequent induction of cell- and complement-mediated cytotoxicity. In clinical trials, 114 (85%) patients treated in the dinutuximab/RA group experienced pain despite pre­-treatment with analgesics including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients in the dinutuximab/RA group compared to 5 (5%) patients in the RA group. Pain typically occurred during the dinutuximab infusion and was most commonly reported as abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, and arthralgia.
MetabolismNA
AbsorptionNA
Volume of Distribution5.4 L
ClearanceThe clearance is 0.21 L/day and increases with body size
CategoriesAntibody, Immunosuppresive agent, Antineoplastic agent
Patents NumberUS20140170155
Date of Issue18/02/14
Date of Expiry18/02/38
Drug InteractionSeverity of adverse effect can be increased while combining Dinutuximab with Acebutolol, Acetazolamide, Acetyldigitoxin, Aldesleukin, Aliskiren, Amifostine, Amiloride, Amiodarone, Amlodipine etc
TargetGanglioside GD2 (small molecule)
Information of corresponding available drug in the market
Brand Nameunituxin
CompanyNA
Brand DiscriptionUnituxin (dinutuximab) is a chimeric monoclonal antibody composed of murine variable heavy and light chain regions and the human constant region for the heavy chain IgG1 and light chain kappa. Unituxin binds to the glycolipid disialoganglioside (GD2). Dinutuximab is produced in the murine myeloma cell line, SP2/0.
Prescribed forUnituxin (dinutuximab) is indicated, in combination with granulocyte- macrophage colony - stimulating factor (GM- CSF), interleukin- 2 (IL- 2) and 13- cis -retinoic acid (RA ), for the treatment of pediatric patients with high- risk neuroblastoma who achieve at least a partial response to prior first -line multiagent, multimodality therapy.
Chemical NameNA
Formulation1 mL of concentrate contains 3.5 mg of dinutuximab
Physcial Appearancesterile, preservative-free, clear/colorless to slightly opalescent solution
Route of AdministrationIntravenous
Recommended DosageThe recommended dose of Unituxin is 17.5 mg/m2/day administered as an intravenous infusion over 10 to 20 hours for 4 consecutive days for a maximum of 5 cycles.
ContraindicationHistory of anaphylaxis to dinutuximab.
Side EffectsThe most common serious adverse reactions (≥ 5%) are infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome.
Useful Linkhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125516s000lbl.pdf , http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002800/WC500192791.pdf , https://www.drugbank.ca/drugs/DB09077
PubMed ID25940913, 24295643, 1988079, 15923178
3-D StructureN.A.