Panitumumab
Encyclopedia
Panitumumab 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.
with disease progression" despite prior treatment. 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.
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 cell
s 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.
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).
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
(also known as EGF receptor, EGFR, ErbB-1 and HER1 in humans).
Panitumumab is manufactured by Amgen
Amgen
Amgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
and marketed as Vectibix. It was originally developed by Abgenix Inc.
Uses
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 cancerColorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
with disease progression" despite prior treatment. Panitumumab was approved by the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
(EMEA) in 2007, and by Health Canada
Health Canada
Health Canada is the department of the government of Canada with responsibility for national public health.The current Minister of Health is Leona Aglukkaq, a Conservative Member of Parliament appointed to the position by Prime Minister Stephen Harper.-Branches, regions and agencies:Health Canada...
in 2008 for "the treatment of refractory EGFR-expressing metastatic colorectal cancer in patients with non-mutated (wild-type) KRAS
KRAS
GTPase KRas also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog and KRAS, is a protein that in humans is encoded by the KRAS gene. Like other members of the Ras family, the KRAS protein is a GTPase and is an early player in many signal transduction pathways...
".
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
Cetuximab
Cetuximab is a chimeric monoclonal antibody, an epidermal growth factor receptor inhibitor, given by intravenous infusion for treatment of metastatic colorectal cancer and head and neck cancer.- Distribution :Cetuximab is manufactured and distributed in North America by ImClone and Bristol-Myers...
) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations.
Mechanism
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.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 cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s that produced an antibody against EGFR was selected and immortalized in Chinese hamster ovary (CHO) cells
Chinese Hamster Ovary cell
Chinese hamster ovary cells are a cell line derived from the ovary of the Chinese hamster. They are often used in biological and medical research and commercially in the production of therapeutic proteins. They were introduced in the 1960s and grow as a cultured monolayer...
. These cells are then used for the full scale manufacture of the 100% human antibody.
Panitumumab vs. cetuximab
Although they both target the EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in their isotypeIsotype (immunology)
An isotype usually refers to any related proteins/genes from a particular gene family. In immunology, the "immunoglobulin isotype" refers to the genetic variations or differences in the constant regions of the heavy and light chains...
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
Antibody-dependent cellular cytotoxicity
Antibody-Dependent Cell-Mediated Cytotoxicity is a mechanism of cell-mediated immunity whereby an effector cell of the immune system actively lyses a target cell that has been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune...
(ADCC).