title: Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells.
abstract: Natural killer cells are key cells of the innate immune system. Natural killer cell receptor repertoires are diversified by a stochastic expression of killer-cell-immunoglobulin-like receptors and lectin-like receptors such as NKG2 receptors. All individuals harbor a subset of natural killer cells expressing NKG2A, the inhibitory checkpoint receptor for HLA-E. Most neoplastic and normal hematopoietic cells express HLA-E, the inhibitory ligand of NKG2A. A novel anti-human NKG2A antibody induced tumor cell death, suggesting that the antibody could be useful in the treatment of cancers expressing HLA-E. We found that immunodeficient mice, co-infused with human primary leukemia or Epstein-Barr virus cell lines and NKG2A(+) natural killer cells, pre-treated with anti-human NKG2A, were rescued from disease progression. Human NKG2A(+) natural killer cells reconstituted in immunodeficient mice after transplantation of human CD34(+) cells. These natural killer cells are able to kill engrafted human primary leukemia or Epstein-Barr virus cell lines by lysis after intraperitoneal administration of anti-human NKG2A. Thus, this anti-NKG2A may exploit the anti-leukemic action of the wave of NKG2A(+) natural killer cells recovering after hematopoietic stem cell transplants or adoptive therapy with natural killer cell infusions from matched or mismatched family donors after chemotherapy for acute leukemia, without the need to search for a natural killer cell alloreactive donor.
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplantation Program, Department of Medicine, University of Perugia, Italy loredana.ruggeri@unipg.it.
authors.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplantation Program, Department of Medicine, University of Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Urbani
authors.affiliation: Innate Pharma, Marseille, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: André
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplantation Program, Department of Medicine, University of Perugia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Mancusi
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplantation Program, Department of Medicine, University of Perugia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tosti
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplantation Program, Department of Medicine, University of Perugia, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Topini
authors.affiliation: Innate Pharma, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bléry
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplantation Program, Department of Medicine, University of Perugia, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Animobono
authors.affiliation: Division of Immunology, University of Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Romagné
authors.affiliation: Innate Pharma, Marseille, France.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Wagtmann
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplantation Program, Department of Medicine, University of Perugia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000037:antagonists & inhibitors*; D000097625:HLA-E Antigens
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D000097625:HLA-E Antigens