title: IPH4102, a humanized KIR3DL2 antibody with potent activity against cutaneous T-cell lymphoma.
abstract: 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.
authors.affiliation: INSERM U976, Hôpital Saint Louis, Paris, France. University Paris Diderot, Sorbonne Paris Cité, UMRS 976, Paris, France. helene.sicard@innate-pharma.fr anne.marie-cardine@inserm.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Marie-Cardine
authors.affiliation: INNATE PHARMA, Marseilles, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Viaud
authors.affiliation: INSERM U976, Hôpital Saint Louis, Paris, France. University Paris Diderot, Sorbonne Paris Cité, UMRS 976, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Thonnart
authors.affiliation: INNATE PHARMA, Marseilles, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Joly
authors.affiliation: INNATE PHARMA, Marseilles, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chanteux
authors.affiliation: INNATE PHARMA, Marseilles, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gauthier
authors.affiliation: INNATE PHARMA, Marseilles, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Bonnafous
authors.affiliation: INNATE PHARMA, Marseilles, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rossi
authors.affiliation: INNATE PHARMA, Marseilles, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bléry
authors.affiliation: INNATE PHARMA, Marseilles, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Paturel
authors.affiliation: INSERM U976, Hôpital Saint Louis, Paris, France. University Paris Diderot, Sorbonne Paris Cité, UMRS 976, Paris, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.affiliation: INSERM U976, Hôpital Saint Louis, Paris, France. University Paris Diderot, Sorbonne Paris Cité, UMRS 976, Paris, France. AP-HP, Hôpital Saint Louis, Department of Dermatology, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.affiliation: INNATE PHARMA, Marseilles, France. helene.sicard@innate-pharma.fr anne.marie-cardine@inserm.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Sicard
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009367:Neoplasm Staging; D054347:Receptors, KIR3DL2 / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C515084:KIR3DL2 protein, human; D054347:Receptors, KIR3DL2