Abstract 4733: Novel therapeutic and diagnostic antibodies against KIR3DL2, a unique tumor antigen overexpressed on subtypes of T Cell Lymphomas .

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC KIR3DL2belongs to the killer immunoglobulin (Ig)-like receptors (KIRs) family and is composed of three extracellular Ig-like domains. KIR3DL2is naturally expressed on some NK cells and minor subpopulations of CD8+ and CD4+ T cells. Physiologically, KIRD3L2 is an inhibitory receptor for human leukocyte antigen (HLA) class I molecules regulating NK cell activation. Remarkably, KIR3DL2is also aberrantly overexpressed on several subtypes of T lymphomas/leukemias, such as Sezary Syndrome, transformed Mycosis Fungoidesand HTLV1+ Adult T Cell Leukemia, making it a unique therapeutic target in cancer. We have generated a series of anti- KIR3DL2monoclonal antibodies (mAbs) binding selectivelyto KIR3DL2, spanning epitopes on each of the three Ig domains. Their efficacy was evaluated in vitro and in vivo against KIR3DL2-expressing tumors and Sezary cell lines as disease model. Various modes of action, such as complement-dependent cytotoxicity(CDC) and antibody-dependent cell cytotoxicity(ADCC) were found involved in their anti-tumor activity. In parallel, anti- KIR3DL2mAbs were also developed as unique and sensitive tools for the detection by immunohistochemistry of KIR3DL2on tumor biopsies. Owing to the promising efficacy profile of our anti- KIR3DL2mAb candidates and to the highly restricted expression pattern of the target on some T leukemia/lymphoma cells, an antibody-based therapy targeting KIR3DL2stands as a potentially unequalled strategy in several orphan diseaseswith critical unmet medical need. Citation Format: Nicolas Viaud, Nathalie Granier, Stephanie Zerbib, Arnaud Dujardin, Cecile Bonnafous, Mathieu Blery, CarinePaturel, Benjamin Rossi, Anne Marie-Cardine, Armand Bensussan, Martine Bagot, Helene Sicard. Novel therapeutic and diagnostic antibodies against KIR3DL2, a unique tumor antigenoverexpressed on subtypes of T Cell Lymphomas . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4733. doi:10.1158/1538-7445.AM2013-4733