Therapeutic anti-IgE antibodies generate distinct functional immune complex signatures
- 1Inselspital Bern, University of Bern
Abstract
Therapeutic IgG anti-IgE antibodies are benchmarked by their ability to interfere with IgE-Fc[epsilon]RI binding, but their activity within IgE and IgG-containing immune complexes remains poorly defined. Here we show that omalizumab and ligelizumab form binary IgE-IgG and ternary allergen-containing immune complexes with distinct functional properties. In primary human leukocytes, these complexes exhibited antibody- and composition-dependent patterns of cellular association and activation. Using multiplexed focal molography, we resolved Fc receptor engagement across free and complexed antibody states and identified distinct receptor-binding signatures for omalizumab- and ligelizumab-containing complexes. Notably, allergen incorporation reversed the relative ability of the two antibodies to neutralize IgE-Fc[epsilon]RI interactions and remodelled Fc[gamma]R binding. Thus, immune-complex composition is a determinant of therapeutic antibody function.
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BibTeX
@misc{navarro2026therapeutic,
title = {{Therapeutic anti-IgE antibodies generate distinct functional immune complex signatures}},
author = {M. Miro Navarro and A. G. Geiger and S. Notova and A. Frutiger and M. F. Bachmann and P. Engeroff},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.764804},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.764804v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Therapeutic anti-IgE antibodies generate distinct functional immune complex signatures
AU - M. Miro Navarro
AU - A. G. Geiger
AU - S. Notova
AU - A. Frutiger
AU - M. F. Bachmann
AU - P. Engeroff
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.764804
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.764804v1
AB - Therapeutic IgG anti-IgE antibodies are benchmarked by their ability to interfere with IgE-Fc[epsilon]RI binding, but their activity within IgE and IgG-containing immune complexes remains poorly defined. Here we show that omalizumab and ligelizumab form binary IgE-IgG and ternary allergen-containing immune complexes with distinct functional properties. In primary human leukocytes, these complexes exhibited antibody- and composition-dependent patterns of cellular association and activation. Using multiplexed focal molography, we resolved Fc receptor engagement across free and complexed antibody states and identified distinct receptor-binding signatures for omalizumab- and ligelizumab-containing complexes. Notably, allergen incorporation reversed the relative ability of the two antibodies to neutralize IgE-Fc[epsilon]RI interactions and remodelled Fc[gamma]R binding. Thus, immune-complex composition is a determinant of therapeutic antibody function.
ER -