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
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...
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doaj-90203a981820425d90aa6193a4e80d5c2021-01-10T12:10:31ZengBMCJournal of Nanobiotechnology1477-31552021-01-0119111210.1186/s12951-020-00752-wDouble attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab-mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activityKai-Wen Ho0I.-J.u Chen1Yi-An Cheng2Tzu-Yi Liao3En-Shuo Liu4Huei-Jen Chen5Yun-Chi Lu6Yu-Cheng Su7Steve R. Roffler8Bo-Cheng Huang9Hui-Ju Liu10Ming-Yii Huang11Chiao-Yun Chen12Tian-Lu Cheng13Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityDrug Development and Value Creation Research Center, Kaohsiung Medical UniversityDrug Development and Value Creation Research Center, Kaohsiung Medical UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityDrug Development and Value Creation Research Center, Kaohsiung Medical UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityDrug Development and Value Creation Research Center, Kaohsiung Medical UniversityDepartment of Biomedical Science and Environmental Biology, Kaohsiung Medical UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityDepartment of Biomedical Science and Environmental Biology, Kaohsiung Medical UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityDrug Development and Value Creation Research Center, Kaohsiung Medical UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityAbstract 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.https://doi.org/10.1186/s12951-020-00752-wBispecific antibody (CD20 ab-mPEG scFv)Liquid tumorsInternalizationPegylated nanoparticleSpecific targeting |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 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 Journal of Nanobiotechnology Bispecific antibody (CD20 ab-mPEG scFv) Liquid tumors Internalization Pegylated nanoparticle Specific targeting |
author_facet |
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 |
author_sort |
Kai-Wen Ho |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
BMC |
series |
Journal of Nanobiotechnology |
issn |
1477-3155 |
publishDate |
2021-01-01 |
description |
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. |
topic |
Bispecific antibody (CD20 ab-mPEG scFv) Liquid tumors Internalization Pegylated nanoparticle Specific targeting |
url |
https://doi.org/10.1186/s12951-020-00752-w |
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