Antibody-Dependent Cellular Phagocytosis by Macrophages is a Novel Mechanism of Action of Elotuzumab. 2018

Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Elotuzumab, a recently approved antibody for the treatment of multiple myeloma, has been shown to stimulate Fcγ receptor (FcγR)-mediated antibody-dependent cellular cytotoxicity by natural killer (NK) cells toward myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody-dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to antitumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor-associated macrophages using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant antitumor efficacy of single-agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc-FcγR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in vivo and mediates ADCP of myeloma cells though a FcγR-dependent manner in vitro Together, these findings propose a novel immune-mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity. Mol Cancer Ther; 17(7); 1454-63. ©2018 AACR.

UI MeSH Term Description Entries
D007694 Killer Cells, Natural Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type. NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009101 Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY. Myeloma, Plasma-Cell,Kahler Disease,Myeloma, Multiple,Myeloma-Multiple,Myelomatosis,Plasma Cell Myeloma,Cell Myeloma, Plasma,Cell Myelomas, Plasma,Disease, Kahler,Multiple Myelomas,Myeloma Multiple,Myeloma, Plasma Cell,Myeloma-Multiples,Myelomas, Multiple,Myelomas, Plasma Cell,Myelomas, Plasma-Cell,Myelomatoses,Plasma Cell Myelomas,Plasma-Cell Myeloma,Plasma-Cell Myelomas
D010587 Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES). Phagocytoses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000920 Antibody-Dependent Cell Cytotoxicity The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. ADCC,Cytotoxicity, Antibody-Dependent Cell,Cell Cytoxicity, Antibody-Dependent,Antibody Dependent Cell Cytotoxicity,Antibody-Dependent Cell Cytotoxicities,Antibody-Dependent Cell Cytoxicities,Antibody-Dependent Cell Cytoxicity,Cell Cytotoxicities, Antibody-Dependent,Cell Cytotoxicity, Antibody-Dependent,Cell Cytoxicities, Antibody-Dependent,Cell Cytoxicity, Antibody Dependent,Cytotoxicities, Antibody-Dependent Cell,Cytotoxicity, Antibody Dependent Cell,Cytoxicities, Antibody-Dependent Cell,Cytoxicity, Antibody-Dependent Cell
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

Related Publications

Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
May 2019, Journal of immunological methods,
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
December 2015, Cancer research,
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
January 1983, The American journal of tropical medicine and hygiene,
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
January 2021, Biomaterials,
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
November 1989, The Journal of clinical investigation,
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
August 2020, BMB reports,
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
January 1985, Cellular immunology,
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
January 2022, Methods in molecular biology (Clifton, N.J.),
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
February 1999, Breast cancer research and treatment,
Ahmed T Kurdi, and Siobhan V Glavey, and Natalie A Bezman, and Amy Jhatakia, and Jennifer L Guerriero, and Salomon Manier, and Michele Moschetta, and Yuji Mishima, and Aldo Roccaro, and Alexandre Detappe, and Chia-Jen Liu, and Antonio Sacco, and Daisy Huynh, and Yu-Tzu Tai, and Michael D Robbins, and Jamil Azzi, and Irene M Ghobrial
January 2019, Frontiers in immunology,
Copied contents to your clipboard!