Probing the interaction between cisplatin and the therapeutic monoclonal antibody trastuzumab

Abstract

Trastuzumab (Herceptin) is a fully humanized monoclonal immunoglobulin γ-1 (IgG1) antibody directed against the HER2/neu receptor, which is up-regulated in about 20–25% of gastric and breast cancer patients. The combination of trastuzumab with cisplatin results in a favourable toxicity profile in the case of advanced HER2-positive gastric and gastroesophageal cancers, gaining the approval by the U.S. FDA in 2010. However, the current literature reveals no atomic details about platinum drug–trastuzumab interactions, probably because of size limitations. Our research aim has been to probe the interaction between the monoclonal antibody trastuzumab and cisplatin by means of electrospray mass spectrometry analysis within the “divide and conquer” approach and ¹H, ¹⁵N-HSQC NMR spectroscopy (using ¹⁵N-labeled cisplatin). We demonstrate that trastuzumab is able to bind platinum and that there is no involvement of the residues belonging to the antigen-binding region so that the receptor recognition is not affected.