Panitumumab
- CAS Number: 339177-26-3
Panitumumab ( Vectibix ® trade name, manufacturer, Amgen ) is a human monoclonal antibody from the group of immunoglobulins IgG2κ. It binds to the receptor of proliferation factor EGF ( epidermal growth factor ), a protein that plays an important role in the signal transduction of cells. By binding to the EGF receptor panitumumab downstream signaling is blocked and inhibited the proliferation of the cell. Compared to chimeric antibodies (for example, which is also directed against the EGFR cetuximab) and humanized antibody panitumumab does not contain foreign protein moieties that can be recognized by the body's immune system as a foreign protein.
Indication and Development
Panitumumab is approved as monotherapy for the treatment of metastatic, EGFR -expressing colorectal carcinoma with non- mutated (wild-type ) KRAS gene in patients in whom fluoropyrimidine -, oxaliplatin -, and irinotecan - containing chemotherapy regimens have failed.
The goal of the development of a complete human monoclonal antibody has been to achieve an efficient and targeted therapy at reduced risk of immune responses. Panitumumab was developed by the biotechnology company Abgenix means of the so-called Xeno - Mouse technology in 2002. Patent rights commitments in respect since the acquisition of Abgenix in 2006, the biotechnology company Amgen. The specificity of this antibody is that it does not xenogeneic (ie, species- foreign ) shares has - that is fully human - and therefore has a low immunogenicity.
For the first time the influence of the KRAS gene was in the panitumumab trial ( mutated versus non- mutated ) detected on the treatment outcome of EGFR antibodies. The data showed that only patients ( 60 %) benefited from treatment with panitumumab whose tumors exhibited a non- mutated KRAS gene (wild type). The KRAS protein is involved in the EGFR signaling cascade downstream ( downstream) of the EGF receptor. This gene is mutated, which has a functionally modified protein to the sequence ( constitutively active), that is, the transmission signal is always active, even if it was above the receptor blocked. Tumors with mutated KRAS gene, therefore, do not respond to anti -EGFR therapy, such as panitumumab. Meanwhile KRAS is established in metastatic colorectal carcinoma as an oncogene with predictive significance.
Admission
In the U.S., panitumumab was approved in September 2006. In the European Union it was approved in December 2007 as a monotherapy for the treatment of metastatic, EGFR -expressing colorectal carcinoma with non- mutated (wild-type ) KRAS gene in patients in whom fluoropyrimidine -, oxaliplatin -, and irinotecan chemotherapy regimens have failed.
In September 2009, results of two large phase III studies made ( the first prospective KRAS data included ) the effectiveness of Vectibix ® in combination with chemotherapy ( 1st and 2nd line therapy ) significantly. In the EMA, therefore, the application for extension of indication for the combination with chemotherapy was provided in April 2010.
Side effects and limitations of use
The most common adverse effects were reported skin reactions, gastrointestinal disorders such as diarrhea, nausea, vomiting and constipation, also abdominal pain, fatigue, and metabolic and nutritional disorders. Severe side effects such as corneal firings of the eye ( keratitis ) occurred in rare cases, but more often severe inflammatory disease of the skin or connective tissue ( fasciitis ). In colorectal cancer with mutated KRAS gene Panitumumab is not effective and has in combination with certain other chemotherapeutic agents ( FOLFOX ) even have a detrimental effect, which is why the determination of KRAS status is significant.