Efficient carcinoma cell killing by activated polymorphonuclear neutrophils targeted with an Ep-CAMxCD64 (HEA125x197) bispecific antibody.
Bispecific antibodies (bsAb) have attracted much attention over the past several years as a mean to improve immunotherapy of cancer. Due to their dual specificity, bsAb are able to redirect effector cells against tumor targets. In this study, the development and preclinical testing of a new quadroma-derived bsAb, HEA125x197, recognizing the tumor-associated Ep-CAM antigen and the high affinity Fc receptor for IgG, CD64, is reported. Using granulocyte-colony stimulating factor (G-CSF) and interferon-gamma (IFN-gamma)-stimulated polymorphonuclear neutrophils to induce CD64 expression, bsAb HEA125 x 197 elicited strong cytotoxic activity towards allogeneic and autologous ovarian carcinoma cells. The cytolytic efficiency of this antibody was comparable to that of a previously described bsAb, HEA125 x OKT3, targeting preactivated T lymphocytes against Ep-CAM-carrying tumor cells. Based on the pan-carcinoma specificity and the stable expression of Ep-CAM, bsAb HEA125x197 may broaden the spectrum of bispecific reagents for the treatment of epithelial malignancies.
Schweizer
Christof
C
Department of Molecular Immunology (G0400), German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Strauss
Gudrun
G
Lindner
Matthias
M
Marmé
Alexander
A
Deo
Yashwant M
YM
Moldenhauer
Gerhard
G
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D009504:Neutrophils / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D017452:Receptors, IgG / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D017452:Receptors, IgG