Role of IgE receptors in IgE antibody-dependent cytotoxicity and phagocytosis of ovarian tumor cells by human monocytic cells.
Antibodies directed against tumor-associated antigens are emerging as effective treatments for a number of cancers, although the mechanism(s) of action for some are unclear and still under investigation. We have previously examined a chimeric IgE antibody (MOv18 IgE), against the ovarian tumor-specific antigen, folate binding protein (FBP), and showed that it can direct human PBMC to kill ovarian cancer cells. We have developed a three-color flow cytometric assay to investigate the mechanism by which IgE receptors on U937 monocytes target and kill ovarian tumor cells. U937 monocytes express three IgE receptors, the high-affinity receptor, FcepsilonRI, the low-affinity receptor, CD23, and galectin-3, and mediate tumor cell killing in vitro by two mechanisms, cytotoxicity, and phagocytosis. Our results suggest that CD23 mediates phagocytosis, which is enhanced by upregulation of CD23 on U937 cells with IL-4, whereas FcepsilonRI mediates cytotoxicity. We show that effector : tumor cell bridging is associated with both activities. Galectin-3 does not appear to be involved in tumor cell killing. U937 cells and IgE exerted ovarian tumor cell killing in vivo in our xenograft model in nude mice. Harnessing IgE receptors to target tumor cells suggests the potential of tumor-specific IgE antibodies to activate effector cells in immunotherapy of ovarian cancer.
Randall Division of Cell and Molecular Biophysics, King's College London, Room 3.8, New Hunt's House, Guy's Campus, St Thomas's Street, London, SE1 1UL, UK. sophia.karagiannis@kcl.ac.uk
Sophia N
SN
Karagiannis
Marguerite G
MG
Bracher
Rebecca L
RL
Beavil
Andrew J
AJ
Beavil
James
J
Hunt
Natalie
N
McCloskey
Richard G
RG
Thompson
Nicholas
N
East
Frances
F
Burke
Brian J
BJ
Sutton
David
D
Dombrowicz
Frances R
FR
Balkwill
Hannah J
HJ
Gould
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000502:physiology*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000628:therapy*; D010587:Phagocytosis / Q000502:physiology*; D017455:Receptors, IgE / Q000276:immunology*
D017455:Receptors, IgE