Panitumumab

drugbox-mab


source = Human recombinant
target = EGFR
CAS_number = 339177-26-3
ATC_prefix = L01
ATC_suffix = XC08
PubChem =
DrugBank =
C=6306 | H=9732 | N=1672 | O=1994 | S=46
molecular_mass= 147 kDa
bioavailability =
protein_bound =
metabolism =
excretion =
elimination_half-life = ∼7.5 days (range: 4-11 days)
pregnancy_category =
legal_status = Rx-only
routes_of_administration = intravenous

Panitumumab (INN), also 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.

Uses

It was FDA approved for the first time in September 2006, for the "the treatment of EGFR-expressing metastatic colorectal cancer with disease progression" despite prior treatment [" U. S. Food and Drug Administration" [http://www.fda.gov/cder/foi/label/2006/125147s0000lbl.pdf] ] . Panitumumab was approved by the European Medicines Agency (EMA) in 2007, and by Health Canada in 2008 for the treatment of refractory EGFR-expressingmetastatic colorectal cancer in patients with non-mutated (wild-type) KRAS.

Mechanism

:mainarticle|epidermal growth factor receptorEGFR is a transmembrane protein.

Panitumumab works by binding to the extracellular domain of the EGFR (epidermal growth factor receptor) preventing its activation. This in turn, results in halting of the cascade of intracellular signals dependent on this receptor. [cite book |first=Jack W. |last=Plunkett |title=Plunkett's Biotech & Genetics Industry Almanac 2006 | publisher=Plunkett Research, Ltd. | date=September 30, 2005 |ISBN=1593920334 | accessdate=2006-10-20 | language=English ]

Production

Panitumumab is produced 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 antibody.

Panitumumab vs. cetuximab

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 ADCC (antibody-dependent cellular cytotoxicity) better than their IgG2 counterparts, hence although they have not been documented, differences in the responses in treatments with these two antibodies might be expected. [ [http://www.healthvalue.net/IgG1_IgG2.html IgG1_IgG2 ] ]

History

Bevacizumab was the first fully human antibody to EGFR.Fact|date=September 2008

References

Further reading

Philippe Rougier, Emmanuel Mitry, Sophie Dominguez. Les Cancers Digestifs ; Springer , September 1, 2006, page=291 ; language=French