2051-1426-1-S1-P45 2051-1426 Poster presentation <p>Novel therapeutic and diagnostic antibodies against KIR3DL2, a unique tumor antigen overexpressed on subtypes of T cell lymphomas</p> Marie-CardineAnne ViaudNicolas DujardinArnaud RachelJoly GranierNathalie GauthierLaurent BonnafousCecile BleryMathieu PaturelCarine BensussanArmand BagotMartine SicardHelene

R&D, Innate Pharma, Marseille, France

INSERM U976, Hopital St Louis, Paris, France

Journal for ImmunoTherapy of Cancer <p>Abstracts of the 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)</p>Carl RubyThis supplement has not been sponsored. The Supplement Editor declares that he has no competing interests.Meeting abstracts<p>Society for Immunotherapy of Cancer 28th Annual Meeting</p>National Harbor, MD, USA8-10 November 2013www.sitcancer.org/20132051-1426 2013 1 Suppl 1 P45 http://www.immunotherapyofcancer.org/content/1/S1/P45 10.1186/2051-1426-1-S1-P45
7112013 2013Marie-Cardine et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

KIR3DL2 belongs to the killer immunoglobulin (Ig)-like receptors (KIRs) family and is composed of three extracellular Ig-like domains. KIR3DL2 is 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, KIR3DL2 is also aberrantly overexpressed on several subtypes of T lymphomas/leukemias, such as Sezary Syndrome, transformed Mycosis Fungoides and HTLV1+ Adult T Cell Leukemia, making it a unique therapeutic target in cancer. We have generated a series of anti-KIR3DL2 monoclonal antibodies (mAbs) binding selectively to KIR3DL2, spanning epitopes on all three Ig domains. Their efficacy was evaluated in vitro and in vivo against KIR3DL2-expressing tumors and Sezary cell lines as disease model. An autologous assay was set up to evaluate the killing of primary Sezary cells by patients’ NK effectors in the presence of those mAbs. Potent antibody-dependent cell cytotoxicity (ADCC) was found the main mode of action involved in their anti-tumor activity. The most promising candidates were humanized as IgG1 mAbs and the final lead molecule was selected for further development, based on several predefined criteria. In parallel, anti-KIR3DL2 mAbs were also developed as unique and sensitive tools for the detection by immunohistochemistry of KIR3DL2 on tumor biopsies. Owing to the promising efficacy profile of our anti-KIR3DL2 mAb candidate and to the highly restricted expression pattern of the target on some T leukemia/lymphoma cells, an antibody-based therapy targeting KIR3DL2 stands as a potentially unequalled strategy in several orphan diseases with critical unmet medical need.