Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy.
Int J Nanomedicine
; 13: 3189-3201, 2018.
Article
en En
| MEDLINE
| ID: mdl-29881272
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 ANDMETHODS:
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.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
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Antígeno Carcinoembrionario
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Complejo CD3
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Anticuerpos Biespecíficos
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Inmunoterapia
Idioma:
En
Revista:
Int J Nanomedicine
Año:
2018
Tipo del documento:
Article