Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

Abstract

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.

Authors: Pan H1,2, Liu J1,2, Deng W1,2, Xing J1,2, Li Q1,2, Wang Z1,2.

Influence Factor: 4.37

Citation: Int J Nanomedicine 13, 3189-3201 (2018).

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