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LFA102*
Exploratory; Phase I/II (Confirmatory)
Anti-PRLR monoclonal antibody
Solid
LFA102 is a PRLR antagonist monoclonal antibody. Areas of Research: Prostate cancer and breast cancer.

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.

MOA data is based on in vitro/in vivo data. Clinical benefit is unknown.
LFA102 is an investigational compound. Efficacy and safety have not been established.
There is no guarantee LFA102 will become commercially available.
*Subject to an agreement between Novartis Pharmaceuticals Corporation and Xoma.
References
  1. Acosta JJ, Munoz RM, Gonzalez L, et al. Src mediates prolactin-dependent proliferation of T47D and MCF7 cells via the activation of focal adhesion kinase/Erk1/2 and phosphatidylinositol 3-kinase pathways. Mol Endocrinol. 2003;17(11):2268–2282.
  2. Rouet V, Bogorad RL, Kayser K, et al. Local prolactin is a target to prevent expansion of basal/stem cells in prostate tumors. Proc Natl Acad Sci USA. 2010;107(34):15199–15204.
  3. Rose-Hellekant TA, Arendt LM, Schroeder MD, et al. Prolactin induces ER alpha-positive and ER alpha-negative mammary cancer in transgenic mice. Oncogene. 2003;22(30):4664–4674.
  4. Tworoger SS, Hankinson SE. Prolactin and breast cancer etiology: an epidemiologic perspective. J Mammary Gland Biol Neoplasia. 2008;13(1):41–53.
  5. Damiano J, et al. Preclinical development of LFA102, a highly potent and selective neutralizing antibody against the prolactin receptor. In: Proceedings from the 102nd Annual Meeting of the American Association for Cancer Research (AACR); April 2-6, 2011; Orlando, FL. Abstract DT02-02.
  6. Novartis, data on file, 2011.
  7. National Institutes of Health (NIH). ClinicalTrials.gov. http://clinicaltrials.gov/ct2/show/NCT01338831. Updated August 31, 2011. Accessed October 25, 2011.

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.

The search results, details, and descriptions of clinical trials viewed in this app are supplied by ClinicalTrials.gov and EUtrialregistry.com. This information is maintained by a third party over whom Novartis Pharmaceuticals Corporation has no control. As such, Novartis Pharmaceuticals Corporation does not guarantee the accuracy, completeness, adequacy, or any other aspect of the information contained on this site.