Panitumumab

From Wikipedia, the free encyclopedia
  (Redirected from ABX-EGF)
Jump to: navigation, search
Panitumumab ?
Monoclonal antibody
Type Whole antibody
Source Human
Target EGFR
Clinical data
Trade names Vectibix
AHFS/Drugs.com monograph
MedlinePlus a607066
Legal status Prescription only
Routes intravenous
Pharmacokinetic data
Half-life ∼7.5 days (range: 4-11 days)
Identifiers
CAS number 339177-26-3 YesY
ATC code L01XC08
DrugBank DB01269
UNII 6A901E312A YesY
ChEMBL CHEMBL1201827 N
Chemical data
Formula C6398H9878N1694O2016S48 
 N (what is this?)  (verify)

Panitumumab (INN), formerly ABX-EGF, is a fully human monoclonal antibody specific to the epidermal growth factor receptor (also known as EGF receptor, EGFR, ErbB-1 and HER1 in humans).

Panitumumab is manufactured by Amgen and marketed as Vectibix. It was originally developed by Abgenix Inc.

In 2014, Amgen and Illumina entered into an agreement to develop a companion diagnostic to accompany panitumumab.[1]

Uses[edit]

It was approved by the U.S. Food and Drug Administration (FDA) for the first time in September 2006, for "the treatment of EGFR-expressing metastatic colorectal cancer with disease progression" despite prior treatment.[2] Panitumumab was approved by the European Medicines Agency (EMEA) in 2007, and by Health Canada in 2008 for "the treatment of refractory EGFR-expressing metastatic colorectal cancer in patients with non-mutated (wild-type) KRAS".

Panitumumab was the first monoclonal antibody to demonstrate the use of KRAS as a predictive biomarker.

In July 2009, the FDA updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab and cetuximab) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations.[3]

Mechanism[edit]

EGFR is a transmembrane protein. Panitumumab works by binding to the extracellular domain of the EGFR preventing its activation. This results in halting of the cascade of intracellular signals dependent on this receptor.[4]

Panitumumab was developed by immunization of transgenic mice (XenoMouse) that are able to produce human immunoglobulin light and heavy chains. After immunization of these animals a specific clone of B cells that produced an antibody against EGFR was selected and immortalized in Chinese hamster ovary (CHO) cells. These cells are then used for the full scale manufacture of the 100% human antibody.

Panitumumab vs. cetuximab[edit]

Although they both target the EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in their isotype and they might differ in their mechanism of action. Monoclonal antibodies of the IgG1 isotype may activate the complement pathway and mediate antibody-dependent cellular cytotoxicity (ADCC).[5]

References[edit]

  1. ^ "Illumina, Amgen to Develop CDx for Colorectal Cancer". News: Molecular Diagnostics. Gen. Eng. Biotechnol. News (paper) 34 (4). February 15, 2014. p. 32. 
  2. ^ U.S. Food and Drug Administration [1]
  3. ^ OncoGenetics.Org (July 2009). "FDA updates Vectibix and Erbitux labels with KRAS testing info". OncoGenetics.Org. Retrieved 2009-07-20. [dead link]
  4. ^ Plunkett, Jack W. (September 30, 2005). Plunkett's Biotech & Genetics Industry Almanac 2006. Plunkett Research, Ltd. ISBN 1-59392-033-4. 
  5. ^ HealthValue: IgG1 & IgG2

Further reading[edit]

  • Amado, RG; Wolf, M.; Peeters, M.; Van Cutsem, E.; Siena, S.; Freeman, D. J.; Juan, T.; Sikorski, R. et al. (2008). "Wild-Type KRAS is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer". J Clin Onco 26 (10): 1626–1634. doi:10.1200/JCO.2007.14.7116. 
  • Van Cutsem, E; Peeters, M.; Siena, S.; Humblet, Y.; Hendlisz, A.; Neyns, B.; Canon, J.-L.; Van Laethem, J.-L. et al. (2007). "Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer". J Clin Onco 25 (13): 1658–1664. doi:10.1200/JCO.2006.08.1620.