Ladiratuzumab vedotin (SGN-LIV1A) is an ADC (IC 50: 5.6 nM for LIV-1) that targets LIV-1. This compound is composed of a humanized IgG1 monoclonal antibody, linked to MMAE via a protease-cleavable linker. It induces immunogenic cell death (ICD), which triggers an immune response. Ladiratuzumab vedotin is utilized in breast cancer research [1] [2] [3] [4].

Ladiratuzumab vedotin (LIV-1+ cells) triggers an endoplasmic reticulum stress response through ATF6 activation and phosphorylation of IRE1 and eIF2a [3]. It induces ATP and HMGB1 release into the supernatant, marking immunogenic cell death (ICD) [3]. This compound exhibits cytotoxic activity against MCF-7 cells at concentrations of 0-100 ng/mL [4]. When administered at 1 μg/mL for 24 hours, Ladiratuzumab vedotin is internalized, transported to lysosomes, and disrupts the microtubule network in MCF-7 cells [4]. In a cell viability assay using the MCF-7 cell line with concentrations ranging from 0-100 ng/mL over 96 hours, it inhibited cell viability, showing an EC50 value of 6.3 ng/mL [4].

In an MCF-7 breast cancer xenograft model, ladiratuzumab vedotin administered at 3 mg/kg intraperitoneally every four days resulted in tumor regression [4]. Additionally, in the animal model using BALB/C mice (PK analysis) [4], a dose of 3 mg/kg was administered via intravenous injection as a single dose, revealing a terminal half-life of 6.8 days.

Human

Monoclonal, ADC

MMAE