ImClone Systems Inc (formerly IMCL)

[biophud]

New paper in Cancer Cell regarding Matuzumab binding to EGFR.

Some points that I picked up base on my quick read:

1. Cetuximab and Matuzumab bind to distinct and non-overlapping binding sites.

2. Matuzumab does not directly block access of the ligand to the domain III ligand-binding site.

3. Matuzumab blocks the local conformational changes in domain II that are critical high affinity ligand binding and dimerization. The inhibition is non-competitive and the ligand binding site on domain III is not blocked (In contrast to Cetuximab which is a competitive inhibitor that blocks the ligand binding site on domain III).

4. Cetuximab and Matuzumab can bind EGFR simultaneously.

5. The authors of the paper raise the possibilities of a potential synergy if Cetuximab and Matuzumab are administered together.

Comments appreciated,

biophud

PS I wonder if we will ever see this type of structural data from the AMGN/ABGX antibody?