IgE-antibody-dependent immunotherapy of solid tumors: cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells.
Abs have a paramount place in the treatment of certain, mainly lymphoid, malignancies, although tumors of nonhemopoietic origin have proved more refractory ones. We have previously shown that the efficacy of immunotherapy of solid tumors, in particular ovarian carcinoma, may be improved by the use of IgE Abs in place of the conventional IgG. An IgE Ab (MOv18 IgE) against an ovarian-tumor-specific Ag (folate binding protein), in combination with human PBMC, introduced into ovarian cancer xenograft-bearing mice, greatly exceeded the analogous IgG1 in promoting survival. In this study, we analyzed the mechanisms by which MOv18 IgE may exert its antitumor activities. Monocytes were essential IgE receptor-expressing effector cells that mediated the enhanced survival of tumor-bearing mice by MOv18 IgE and human PBMC. Monocytes mediated MOv18 IgE-dependent ovarian tumor cell killing in vitro by two distinct pathways, cytotoxicity and phagocytosis, acting respectively through the IgE receptors FcepsilonRI and CD23. We also show that human eosinophils were potent effector cells in MOv18 IgE Ab-dependent ovarian tumor cell cytotoxicity in vitro. These results demonstrate that IgE Abs can engage cell surface IgE receptors and activate effector cells against ovarian tumor cells. Our findings offer a framework for an improved immunotherapeutic strategy for combating solid tumors.
Karagiannis
Sophia N
SN
Randall Division of Cell and Molecular Biophysics, New Hunt's House, King's College London, Guy's Campus, London, United Kingdom. sophia.karagiannis@kcl.ac.uk
Bracher
Marguerite G
MG
Hunt
James
J
McCloskey
Natalie
N
Beavil
Rebecca L
RL
Beavil
Andrew J
AJ
Fear
David J
DJ
Thompson
Richard G
RG
East
Nicholas
N
Burke
Frances
F
Moore
Robert J
RJ
Dombrowicz
David D
DD
Balkwill
Frances R
FR
Gould
Hannah J
HJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000627:therapeutic use*; D007167:Immunotherapy; D051379:Mice; D009000:Monocytes / Q000276:immunology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D010587:Phagocytosis; D017455:Receptors, IgE / Q000378:metabolism; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C424863:MOv18 monoclonal antibody; D017455:Receptors, IgE; D007073:Immunoglobulin E