title: IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers.
abstract: NK-cell activity against tumor cells is regulated by a complex balance of inhibitory and activating signals, which are mediated by the binding of NK-cell receptors to activating and inhibitory ligands expressed on tumor cells. Thus, the disruption of the inhibitory cascade would shift the balance to activation. IPH-2101 (1-7F9), being developed by Innate Pharma, is a fully human IgG4 anti-killer immunoglobulin-like receptor (KIR) mAb for the treatment of hematological malignancies, such as acute myeloid leukemia (AML) and multiple myeloma (MM). In preclinical studies, IPH-2101 selectively bound to KIR2DL1, 2 and 3, and KIR2DS1 and 2, and exposure of KIR-transfected target cell lines to IPH-2101 led to an augmented NK-cell-mediated lysis. In phase I clinical trials in patients with AML and MM treated with IPH-2101, activation of NK cells was observed and IPH-2101 exhibited a good safety profile. At the time of publication, patients with MM had been recruited to phase II clinical trials to assess single-agent IPH-2101 or IPH-2101 in combination with lenalidomide. These and larger, randomized trials are warranted to clarify whether enhancing a patient's NK-cell activity by IPH-2101 will be a viable approach in the treatment of hematological malignancies.
authors.affiliation: Karolinska Institutet, Karolinska University Hospital Huddinge, Department of Medicine, SE-14186 Stockholm, Sweden. Evren.Alici@ki.se
authors.forename: Evren
authors.initials: E
authors.lastname: Alici
mesh_terms: D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D054340:Receptors, KIR / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell; C558235:IPH-2101