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Updated: Feb 9, 2026

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
Published on: July 12, 2018
Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy
Haitao Pan1,2, Jiayu Liu1,2, Wentong Deng1,2
1School of Pharmaceutical Sciences.
Introduction:
Bispecific antibodies that engage immune cells to kill cancer cells are actively pursued in cancer immunotherapy. Different types of bispecific antibodies, including single-chain fragments, Fab fragments, nanobodies, and immunoglobulin Gs (IgGs), have been studied. However, the low molecular weight of bispecific antibodies with single-chain or Fab fragments generally leads to their rapid clearance in vivo, which limits the therapeutic potential of these bispecific antibodies.
Materials And Methods:
In this study, we used a site-specific PEGylation strategy to modify the bispecific single-domain antibody-linked Fab (S-Fab), which was designed by linking an anticarcinoembryonic antigen (anti-CEA) nanobody with an anti-CD3 Fab.
Results:
The half-life (t1/2) of PEGylated S-Fab (polyethylene glycol-S-Fab) was increased 12-fold in vivo with a slightly decreased tumor cell cytotoxicity in vitro as well as more potent tumor growth inhibition in vivo compared to S-Fab.
Conclusion:
This study demonstrated that PEGylation is an effective approach to enhance the antitumor efficacy of bispecific antibodies.
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