Cancer research · 2014
IPH4102, a humanized KIR3DL2 antibody with potent activity against cutaneous T-cell lymphoma.
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Marie-Cardine Anne, Viaud Nicolas, Thonnart Nicolas, Joly Rachel, Chanteux Stéphanie, Gauthier Laurent, Bonnafous Cécile, Rossi Benjamin, Bléry Mathieu, Paturel Carine, Bensussan Armand, Bagot Martine, Sicard Hélène
Аннотация
Advanced cutaneous T-cell lymphoma (CTCL) remains an unmet medical need, which lacks effective targeted therapies. In this study, we report the development of IPH4102, a humanized monoclonal antibody that targets the immune receptor KIR3DL2, which is widely expressed on CTCL cells but few normal immune cells. Potent antitumor properties of IPH4102 were documented in allogeneic human CTCL cells and a mouse model of KIR3DL2(+) disease. IPH4102 antitumor activity was mediated by antibody-dependent cell cytotoxicity and phagocytosis. IPH4102 improved survival and reduced tumor growth in mice inoculated with KIR3DL2(+) tumors. Ex vivo efficacy was further evaluated in primary Sézary patient cells, sorted natural killer-based autologous assays, and direct spiking into Sézary patient peripheral blood mononuclear cells. In these settings, IPH4102 selectively and efficiently killed primary Sézary cells, including at unfavorable effector-to-target ratios characteristic of unsorted PBMC. Together, our results offer preclinical proof of concept for the clinical development of IPH4102 to treat patients with advanced CTCL.