Compound DescriptionLFA102 is a PRLR antagonist monoclonal antibody
Areas of ResearchProstate cancer and breast cancer
Proposed Mechanism of ActionPRLR is a member of the class I cytokine receptor family (single transmembrane domain) and mediates the physiological effects of the polypeptide hormone prolactin (PRL).
PRLR has no intrinsic enzymatic activity but activates signaling through the Jak-Stat, PI3K-Akt and MEK-ERK1/2 pathways1 leading to cell proliferation and survival. High circulating levels of PRL may be involved with increased breast cancer risk in humans, and genetic experiments in mice have demonstrated a possible link between PRL expression and the development of breast and prostate tumors.2–4
LFA102 is a humanized monoclonal antibody of the IgG1 kappa subtype. This antibody binds to the putative dimerization region of PRLR in a non-ligand competitive manner and inhibits PRL-induced signaling. Preclinical studies suggest multiple potential in vivo mechanisms of action for LFA102: inhibition of PRLR signaling, induction of antibody dependent cell-mediated cytotoxicity (ADCC), and inhibition of tumor angiogenesis.5
Key Preclinical DataPreclinical studies have shown that LFA102 blocks PRL-induced signaling and proliferation in two human cancer cell lines, and abolishes PRL-induced phospho-Stat5 signaling in xenograft tumors.6
LFA102 has also demonstrated to block rat PRLR and is capable of regressing PRL-dependent Nb2-C11 pre-T cell lymphoma tumors in vivo.6
In vitro studies have shown that LFA102 can mediate ADCC and inhibit the PRL-dependent release of the proangiogenic factor vascular endothelial growth factor (VEGF) from breast cancer cells.5
Clinical StatusLFA102 is being investigated in a phase I study in patients with PRLR-positive castration-resistant prostate cancer or PRLR-positive breast cancer.
The information contained herein was last updated on April 12, 2013.
All Compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.
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