Oncotarget

Research Papers:

Generation of a novel Antibody-Drug Conjugate targeting endosialin: potent and durable antitumor response in sarcoma

Emily Capone, Enza Piccolo, Imma Fichera, Paolo Ciufici, Daniela Barcaroli, Arturo Sala, Vincenzo De Laurenzi, Valentina Iacobelli, Stefano Iacobelli _ and Gianluca Sala

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Oncotarget. 2017; 8:60368-60377. https://doi.org/10.18632/oncotarget.19499

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Abstract

Emily Capone1,2, Enza Piccolo1, Imma Fichera1,6, Paolo Ciufici3, Daniela Barcaroli3, Arturo Sala3,4, Vincenzo De Laurenzi2, Valentina Iacobelli1,5, Stefano Iacobelli1,2,* and Gianluca Sala1,2,*

1MediaPharma s.r.l., 66100, Chieti, Italy

2Dipartimento di Scienze Mediche, Orali e Biotecnologiche; University “G. d’Annunzio” Chieti-Pescara, Centro Studi sull’Invecchiamento, CESI-MeT, 66100 - Chieti, Italy

3Dipartimento di Scienze Psicologiche, della Salute e del Territorio, University “G. d’Annunzio” Chieti-Pescara, Centro Studi sull’Invecchiamento, CESI-MeT, 66100 - Chieti, Italy

4College of Health and Life Sciences, Brunel University London, UK

5Department of Gynecology and Obstetrics, University of Rome “La Sapienza”, 00100 - Rome, Italy

6Current address: Nouscom SRL 100 I-00128 Rome, Italy

*These authors share senior authorship

Correspondence to:

Stefano Iacobelli, email: [email protected]

Keywords: endosialin, ADC, sarcoma, duocarmycin, target therapy

Received: May 11, 2017    Accepted: June 19, 2017    Published: July 22, 2017

ABSTRACT

The endosialin/CD248/TEM1 receptor is expressed on the cell surface of tumor-associated stroma cells as well as in sarcoma and neuroblastoma cells. This receptor is emerging as an attractive molecule in diagnostics and therapeutics because of its expression across the stroma of many human tumors, the low to absent expression in normal tissues and accessibility from the vascular circulation. In this study, we present evidence of the preclinical efficacy of a novel Antibody-Drug Conjugate (ENDOS/ADC). It consists of a humanized endosialin monoclonal antibody, named hMP-E-8.3, conjugated to a potent duocarmycin derivative. In endosialin expressing cancer cell lines, this ENDOS/ADC showed a powerful, specific and target-dependent killing activity. High expression levels of endosialin in cells correlated with efficient internalization and cytotoxic effects in vitro. Efficacy studies demonstrated that ENDOS/ADC treatment led to a long-lasting tumor growth inhibition of a cell line-based model of human osteosarcoma. Taken together, our results demonstrate that endosialin is an attractive target in sarcoma and suggest that ENDOS/ADC has the potential to be developed into a bio-therapeutic agent for these malignancies.


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