Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab-mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity

Kai Wen Ho, I. J.u. Chen, Yi An Cheng, Tzu Yi Liao, En Shuo Liu, Huei Jen Chen, Yun Chi Lu, Yu Cheng Su, Steve R. Roffler, Bo Cheng Huang, Hui Ju Liu, Ming Yii Huang, Chiao Yun Chen, Tian Lu Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization. Methods: In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab-mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with an anti-mPEG single chain antibody (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously “grabs” Lipo-Dox® (PEGylated liposomal doxorubicin, PLD) to enhance the cellular internalization and anticancer activity of PLD. Results: We successfully constructed the CD20 Ab-mPEG scFv and proved that CD20 Ab-mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab-mPEG scFv and PLD successfully led to a ninefold increase in tumor cytotoxicity (LC50: 0.38 nM) compared to the CD20 Ab-DNS scFv and PLD (lC50: 3.45 nM) in vitro. Importantly, a combination of CD20 Ab-mPEG scFv and PLD had greater anti-liquid tumor efficacy (P = 0.0005) in Raji-bearing mice than CD20 Ab-DNS scFv and PLD. Conclusion: Our results indicate that this “double-attack” strategy using CD20 Ab-mPEG scFv and PLD can retain the tumor targeting (first attack) and confer PLD tumor-selectivity (second attack) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.[Figure not available: see fulltext.].

Original languageEnglish
Article number16
JournalJournal of Nanobiotechnology
Volume19
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Bispecific antibody (CD20 ab-mPEG scFv)
  • Internalization
  • Liquid tumors
  • Pegylated nanoparticle
  • Specific targeting

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