Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy
| Autor: | Jiayu Liu, Zhong Wang, Haitao Pan, Jieyu Xing, Qing Li, Wentong Deng |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male CD3 Complex half-life medicine.medical_treatment CD3 Biophysics Pharmaceutical Science Bioengineering Antineoplastic Agents Mice SCID Polyethylene Glycols Biomaterials Rats Sprague-Dawley 03 medical and health sciences Immunoglobulin Fab Fragments Immune system CEA Cancer immunotherapy Antigen International Journal of Nanomedicine In vivo Neoplasms Drug Discovery Antibodies Bispecific medicine Animals Humans Fab Original Research biology Chemistry Organic Chemistry PEGylation General Medicine Single-Domain Antibodies Xenograft Model Antitumor Assays Carcinoembryonic Antigen nanobody bispecific antibody 030104 developmental biology Cancer cell Cancer research biology.protein Immunotherapy Antibody |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Haitao Pan,1,2 Jiayu Liu,1,2 Wentong Deng,1,2 Jieyu Xing,1,2 Qing Li,1,2 Zhong Wang1,2 1School of Pharmaceutical Sciences, 2Centre for Cellular & Structural Biology, Sun Yat-Sen University, Guangzhou, People’s Republic of China 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. Keywords: Fab, nanobody, PEGylation, bispecific antibody, half-life, CEA |
| Databáze: | OpenAIRE |
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