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Updated: Aug 28, 2026
A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
Published on: July 12, 2018
Fc-Silenced CD89 × EGFR Bispecific Antibodies Promote Neutrophil and Macrophage Antitumor Activity
Felix Meiser1, Julia Harwardt1, Christoph Hahn2
1Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, 64287 Darmstadt, Germany.
Background/Objectives:
CD89 (FcaRI), the receptor for immunoglobulin A (IgA), is expressed on myeloid cells, including neutrophils, monocytes, and macrophages. It is known to mediate potent effector functions against tumor cells, but the clinical development of IgA-based therapeutics is hindered by manufacturing challenges and IgA's short plasma half-life.
Methods:
Using yeast display, we generated EGFR × CD89 bispecific common light chain antibodies and investigated their biophysical properties, neutrophil-mediated cytotoxicity and macrophage phagocytosis in vitro.
Results:
CD89-targeting constructs induced potent neutrophil cytotoxicity and macrophage phagocytosis in vitro. A symmetric 2 + 2 IgG1 Fc-silenced variant showed the most consistent potency across neutrophil and macrophage effector functions. Fc silencing enhanced neutrophil ADCC and did not induce detectable neutrophil or PBMC fratricide under the conditions tested, suggesting a limited propensity for off-target immune cell killing.
Conclusions:
These findings support further preclinical evaluation of CD89-targeting bispecific antibodies and indicate that Fc silencing may differentially shape neutrophil- and macrophage-mediated antitumor activity.
