Abstract 3620: LIV-1 antibody-drug conjugate: A novel therapeutic agent for breast and prostate cancer

Abstract

Abstract LIV-1, also known as SLC39A6 or ZIP6, is a member of the zinc transporter family and was first identified as an estrogen-inducible gene in breast cancer. LIV-1, as a downstream target of STAT3, promotes the epithelial to mesenchymal transition that is important in the malignant progression to metastasis. Consistent with its role in cancer, we determined by immunohistochemical (IHC) analysis that LIV-1 is expressed by estrogen receptor-positive (ER+), hormone-treated tumors (both primary and metastatic sites) and ER-/PR-/Her2- (triple-negative) breast cancers. Hormone refractory metastatic prostate tumor samples express Liv-1, with expression confirmed in both bone and soft tissue metastatic sites by IHC. In healthy human tissues, LIV-1 expression is limited to hormonally-regulated organs (prostate, uterus, and breast). The broad expression of LIV-1 in prostate and breast cancer tumors in combination with the limited expression in vital organs makes LIV-1 an excellent target for an antibody-drug conjugate (ADC). We generated an ADC consisting of a humanized anti-LIV-1 mAb conjugated to the antitubulin agent monomethyl auristatin E (MMAE), via a plasma stable, enzyme-cleavable linker (vc). The humanized LIV-1 mAb bound with high affinity to both human and cynomolgous LIV-1. In vitro, anti-LIV-1-vcMMAE ADCs showed specific cytotoxic activity against a breast cancer cell line. In vivo studies also demonstrated antitumor activity of anti-LIV-1-vcMMAE ADCs in preclinical xenograft models with significant delay of tumor growth compared to control groups. These findings demonstrate that further evaluation and development of anti-LIV-1-vcMMAE is warranted as a promising and potential therapeutic agent for the treatment of prostate and ER+ and triple-negative breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3620. doi:10.1158/1538-7445.AM2011-3620