Antibody drug conjugates with hydroxamic acid cargos for histone deacetylase (HDAC) inhibition
Claudio Cianferotti, Valentina Faltoni, Elena Cini, Elena Ermini, Francesca Migliorini, Elena Petricci, Maurizio Taddei, Laura Salvini, Gianfranco Battistuzzi, Ferdinando Maria Milazzo, Anna Maria Anastasi, Caterina Chiapparino, Rita De Santis, Giuseppe Giannini
Abstract
Antitumor hydroxamates SAHA and Dacinostat have been linked to cetuximab and trastuzumab through a non-cleavable linker based on the p-mercaptobenzyl alcohol structure. These antibody drug conjugates (ADCs) were able to inhibit HDAC in several tumour cell lines. The cetuximab based ADCs block human lung adenocarcinoma cell proliferation, demonstrating that bioconjugation with antibodies is a suitable approach for targeted therapy based on hydroxamic acid-containing drugs. This work also shows that ADC-based delivery might be used to overcome the classical pharmacokinetic problems of hydroxamic acids.