Comparison of IgE and IgG antibody-dependent cytotoxicity in vitro and in a SCID mouse xenograft model of ovarian carcinoma.
Allergic reactions are mediated by IgE antibodies bound to high-affinity receptors on mast cells in peripheral tissues and are characterized by their immediacy and hypersensitivity. These properties could also be advantageous in immunotherapy against cancer growth in peripheral tissues. We have constructed chimeric IgE and IgG1 antibodies with murine V regions and human C regions corresponding to the MOv18 monoclonal antibody against the human ovarian tumor-associated antigen, folate binding protein. The antibodies exhibited the expected binding affinities for antigen and Fc receptors, and effector activities with human basophils and platelets in vitro. The protective activities of MOv18-IgE and MOv18-IgG1 were compared in a SCID mouse xenograft model of ovarian carcinoma. The beneficial effects of MOv18-IgE were greater and of longer duration than those of MOv18-IgG1. Our results suggest that the allergic reaction could be harnessed for the suppression of ovarian tumors.
Gould
H J
HJ
The Randall Institute King's College London, London, GB. hjg@helios.rai.kcl.ac.uk
Mackay
G A
GA
Karagiannis
S N
SN
O'Toole
C M
CM
Marsh
P J
PJ
Daniel
B E
BE
Coney
L R
LR
Zurawski
V R
VR
Joseph
M
M
Capron
M
M
Gilbert
M
M
Murphy
G F
GF
Korngold
R
R
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D016466:CHO Cells; D002352:Carrier Proteins / Q000276:immunology*; D006224:Cricetinae; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000276:immunology*; D011956:Receptors, Cell Surface; D014183:Transplantation, Heterologous
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D007073:Immunoglobulin E