Probes for PRL

The Prolactin Receptor (PRLR) is a type 1 cytokine receptor that is expressed in a subset of breast cancers and may contribute to its pathogenesis. It is relatively over-expressed in ~25% of human breast tumors while expressed at low levels in some normal human tissues including the mammary gland. We developed an anti-PRLR antibody-drug conjugate (ADC), to target PRLR positive breast cancer. REGN2878-DM1 is comprised of a fully human high affinity function-blocking anti-PRLR IgG1 antibody (REGN2878) conjugated via a non-cleavable SMCC linker to the cytotoxic maytansine derivative DM1. Both unconjugated REGN2878 and conjugated REGN2878-DM1 block PRL mediated activation in vitro and are rapidly internalized into lysosomes. REGN2878-DM1 induces potent cell cycle arrest and cytotoxicity in PRLR-expressing tumor cell lines. In vivo, REGN2878-DM1 demonstrated significant antigen-specific anti-tumor activity against breast cancer xenograft models. In addition, REGN2878-DM1 showed additive activity when combined with the anti-estrogen agent fulvestrant. These results illustrate promising anti-tumor activity against PRLR positive breast cancer xenografts and support the evaluation of anti-PRLR ADCs as potential therapeutic agents in breast cancer.