Oncotarget

Research Papers:

EV20-Sap, a novel anti-HER-3 antibody-drug conjugate, displays promising antitumor activity in melanoma

Emily Capone, Francesco Giansanti, Sara Ponziani, Alessia Lamolinara, Manuela Iezzi, Annamaria Cimini, Francesco Angelucci, Rossana La Sorda, Vincenzo De Laurenzi, Pier Giorgio Natali, Rodolfo Ippoliti, Stefano Iacobelli and Gianluca Sala _

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Oncotarget. 2017; 8:95412-95424. https://doi.org/10.18632/oncotarget.20728

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Abstract

Emily Capone1,*, Francesco Giansanti2,*, Sara Ponziani2,3, Alessia Lamolinara4, Manuela Iezzi4, Annamaria Cimini2,5,6, Francesco Angelucci2, Rossana La Sorda3, Vincenzo De Laurenzi1, Pier Giorgio Natali3, Rodolfo Ippoliti2, Stefano Iacobelli1,3 and Gianluca Sala1,3

1Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy

2Department of Life, Health and Environmental Sciences, University of L'Aquila, Coppito (AQ) Italy

3MediaPharma s.r.l., Via della Colonnetta, Chieti, Italy

4Department of Medicine and Aging Science, Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D’Annunzio University, Chieti-Pescara, Italy

5Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology Temple University, Philadelphia, USA

6National Institute for Nuclear Physics (INFN), Gran Sasso National Laboratory (LNGS), Assergi, Italy

*These authors have contributed equally to this work

Correspondence to:

Gianluca Sala, email: g.sala@unich.it

Stefano Iacobelli, email: iacobell@unich.it

Keywords: HER-3, antibody-drug conjugate, melanoma, saporin, target therapy

Received: June 22, 2017     Accepted: August 08, 2017     Published: September 08, 2017

ABSTRACT

Melanoma is the most biologically aggressive skin cancer of well established constitutive and induced resistance to pharmacological treatment. Despite the recent progresses in immunotherapies, many advanced metastatic melanoma patients still face a significant mortality risk. The aggressive nature of this disease sustains an urgent need for more successful, effective drugs. HER-3 - one of the four member of the tyrosin kinase epidermal growth factor receptors (EGFRs) family- is frequently overexpressed in solid tumors, including melanoma. Moreover, up-regulation of HER-3 and its ligand NRGβ-1 are associated with poor prognosis, thus suggesting this receptor as a suitable target for cancer therapy. Several monoclonal antibodies targeting HER-3 are currently available, but preliminary results from clinical testing of these agents reveal a modest efficacy. Thus, a substantial improvement over this immunotherapeutic approach could be offered by an anti-HER-3 based Antibody-Drug Conjugate (ADC). In the present paper, we describe the generation of an ADC obtained by coupling the HER-3 targeting antibody EV20 linked to the plant toxin Saporin (Sap). In vitro, this ADC displays a powerful, specific and target-dependent cytotoxic activity which correlates with the degree of expression and internalization of HER-3 on tumor cells. Furthermore, in a murine melanoma model, EV20-Sap treatment leads to a significant reduction of the number of pulmonary metastasis.


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