EV20, a Novel Anti-ErbB-3 Humanized Antibody, Promotes ErbB-3 Down-Regulation and Inhibits Tumor Growth In Vivo.
ErbB-3 (HER-3) receptor is involved in tumor progression and resistance to therapy. Development of specific inhibitors impairing the activity of ErbB-3 is an attractive tool for cancer therapeutics. MP-RM-1, a murine monoclonal antibody targeting human ErbB-3, has shown anticancer activity in preclinical models. With the aim to provide novel candidates for clinical use, we have successfully generated a humanized version of MP-RM-1. The humanized antibody, named EV20, abrogates both ligand-dependent and ligand-independent receptor signaling of several tumor cell types, strongly promotes ErbB-3 down-regulation, and efficiently and rapidly internalizes into tumor cells. Furthermore, treatment with EV20 significantly inhibits growth of xenografts originating from prostatic, ovarian, and pancreatic cancers as well as melanoma in nude mice. In conclusion, we provide a novel candidate for ErbB-3-targeted cancer therapy.
MediaPharma srl, Chieti, Italy ; Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Gianluca
G
Sala
Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Ilario Giovanni
IG
Rapposelli
Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy ; Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Reza
R
Ghasemi
MediaPharma srl, Chieti, Italy ; Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Enza
E
Piccolo
MediaPharma srl, Chieti, Italy ; Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Sara
S
Traini
Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Emily
E
Capone
Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Cosmo
C
Rossi
Sigma-Tau Industrie Farmaceutiche Riunite SpA, Pomezia, Italy.
Angela
A
Pelliccia
MediaPharma srl, Chieti, Italy ; Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Annalisa
A
Di Risio
Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Maurizia
M
D'Egidio
MediaPharma srl, Chieti, Italy ; Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Nicola
N
Tinari
MediaPharma srl, Chieti, Italy ; Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Raffaella
R
Muraro
MediaPharma srl, Chieti, Italy ; Department of Experimental and Clinical Sciences, G. D'Annunzio University Foundation, Chieti, Italy.
Stefano
S
Iacobelli