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.
J Nanobiotechnology
; 19(1): 16, 2021 Jan 09.
Article
en En
| MEDLINE
| ID: mdl-33422061
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.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
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Leucemia
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Doxorrubicina
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Anticuerpos Biespecíficos
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Anticuerpos de Cadena Única
Idioma:
En
Revista:
J Nanobiotechnology
Año:
2021
Tipo del documento:
Article