Data from SGN–LIV1A: A Novel Antibody–Drug Conjugate Targeting LIV-1 for the Treatment of Metastatic Breast Cancer

Abstract

<div>Abstract<p>In this article, we describe a novel antibody–drug conjugate (ADC; SGN–LIV1A), targeting the zinc transporter LIV-1 (SLC39A6) for the treatment of metastatic breast cancer. LIV-1 was previously known to be expressed by estrogen receptor–positive breast cancers. In this study, we show that LIV-1 expression is maintained after hormonal therapy in primary and metastatic sites and is also upregulated in triple-negative breast cancers. In addition to breast cancer, other indications showing LIV-1 expression include melanoma, prostate, ovarian, and uterine cancer. SGN–LIV1A consists of a humanized antibody conjugated through a proteolytically cleavable linker to monomethyl auristatin E, a potent microtubule-disrupting agent. When bound to surface-expressed LIV-1 on immortalized cell lines, this ADC is internalized and traffics to the lysozome. SGN–LIV1A displays specific <i>in vitro</i> cytotoxic activity against LIV-1–expressing cancer cells. <i>In vitro</i> results are recapitulated <i>in vivo</i> where antitumor activity is demonstrated in tumor models of breast and cervical cancer lineages. These results support the clinical evaluation of SGN–LIV1A as a novel therapeutic agent for patients with LIV-1–expressing cancer. <i>Mol Cancer Ther; 13(12); 2991–3000. ©2014 AACR</i>.</p></div>