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Pharmaceutics
Volume 13
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10.3390/pharmaceutics13040483
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Article

EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors

by
Emily Capone
1,2,
Rossano Lattanzio
1,2,
Fabio Gasparri
3,
Paolo Orsini
3,
Cosmo Rossi
2,
Valentina Iacobelli
4,
Vincenzo De Laurenzi
1,2,
Pier Giorgio Natali
5,
Barbara Valsasina
3,
Stefano Iacobelli
5,* and
Gianluca Sala
1,2,*
1
Department of Innovative Technologies in Medicine & Dentistry, University of Chieti-Pescara, 66100 Chieti, Italy
2
Center for Advanced Studies and Technology (CAST), Via Polacchi 11, 66100 Chieti, Italy
3
Nerviano Medical Sciences Srl, 20014 Milan, Italy
4
Department of Gynecology and Obstetrics, Catholic University, 00168 Rome, Italy
5
MediaPharma s.r.l., Via della Colonnetta 50/A, 66100 Chieti, Italy
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2021, 13(4), 483; https://doi.org/10.3390/pharmaceutics13040483
Submission received: 26 February 2021 / Revised: 25 March 2021 / Accepted: 30 March 2021 / Published: 2 April 2021
(This article belongs to the Special Issue Antibody–Drug Conjugates (ADC))
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Abstract

HER-3 is becoming an attractive target for antibody–drug conjugate (ADC)-based therapy. Indeed, this receptor and its ligands are found to be overexpressed in several malignancies, and re-activation of its downstream signaling axis is known to play a critical role in modulating the sensitivity of targeted therapeutics in different tumors. In this study, we generated a novel ADC named EV20/NMS-P945 by coupling the anti-HER-3 antibody EV20 with a duocarmycin-like derivative, the thienoindole (TEI) NMS-P528, a DNA minor groove alkylating agent through a peptidic cleavable linker. This ADC showed target-dependent cytotoxic activity in vitro on several tumor cell lines and therapeutic activity in mouse xenograft tumor models, including those originating from pancreatic, prostatic, head and neck, gastric and ovarian cancer cells and melanoma. Pharmacokinetics and toxicological studies in monkeys demonstrated that this ADC possesses a favorable terminal half-life and stability and it is well tolerated. These data support further EV20/NMS-P945 clinical development as a therapeutic agent against HER-3-expressing malignancies.
Keywords: antibody–drug conjugates; HER-3; targeted therapy; duocarmycin antibody–drug conjugates; HER-3; targeted therapy; duocarmycin

Share and Cite

MDPI and ACS Style

Capone, E.; Lattanzio, R.; Gasparri, F.; Orsini, P.; Rossi, C.; Iacobelli, V.; De Laurenzi, V.; Natali, P.G.; Valsasina, B.; Iacobelli, S.; et al. EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors. Pharmaceutics 2021, 13, 483. https://doi.org/10.3390/pharmaceutics13040483

AMA Style

Capone E, Lattanzio R, Gasparri F, Orsini P, Rossi C, Iacobelli V, De Laurenzi V, Natali PG, Valsasina B, Iacobelli S, et al. EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors. Pharmaceutics. 2021; 13(4):483. https://doi.org/10.3390/pharmaceutics13040483

Chicago/Turabian Style

Capone, Emily, Rossano Lattanzio, Fabio Gasparri, Paolo Orsini, Cosmo Rossi, Valentina Iacobelli, Vincenzo De Laurenzi, Pier Giorgio Natali, Barbara Valsasina, Stefano Iacobelli, and et al. 2021. "EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors" Pharmaceutics 13, no. 4: 483. https://doi.org/10.3390/pharmaceutics13040483

APA Style

Capone, E., Lattanzio, R., Gasparri, F., Orsini, P., Rossi, C., Iacobelli, V., De Laurenzi, V., Natali, P. G., Valsasina, B., Iacobelli, S., & Sala, G. (2021). EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors. Pharmaceutics, 13(4), 483. https://doi.org/10.3390/pharmaceutics13040483

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