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

Autor: Tian-Lu Cheng, I-Ju Chen, Yun Chi Lu, Yu-Cheng Su, Tzu Yi Liao, Yi An Cheng, Ming-Yii Huang, Kai Wen Ho, Steve R. Roffler, Huei Jen Chen, En Shuo Liu, Chiao Yun Chen, Hui Ju Liu, Bo Cheng Huang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Pharmaceutical Science
Medicine (miscellaneous)
Mice
SCID
Applied Microbiology and Biotechnology
Polyethylene Glycols
Mice
chemistry.chemical_compound
Drug Delivery Systems
0302 clinical medicine
hemic and lymphatic diseases
Antibodies
Bispecific
Internalization
media_common
CD20
Mice
Inbred BALB C
0303 health sciences
Liposome
Leukemia
biology
Chemistry
Antibodies
Monoclonal
respiratory system
Raji cell
lcsh:R855-855.5
030220 oncology & carcinogenesis
Molecular Medicine
Female
lipids (amino acids
peptides
and proteins)
Antibody
lcsh:Medical technology
media_common.quotation_subject
lcsh:Biotechnology
Biomedical Engineering
Bispecific antibody (CD20 ab-mPEG scFv)
Bioengineering
chemical and pharmacologic phenomena
Ofatumumab
03 medical and health sciences
lcsh:TP248.13-248.65
Liquid tumors
medicine
Animals
Humans
030304 developmental biology
Research
Specific targeting
Pegylated nanoparticle
medicine.disease
In vitro
Doxorubicin
Liposomes
Cancer research
biology.protein
Nanoparticles
Single-Chain Antibodies
Zdroj: Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-12 (2021)
Journal of Nanobiotechnology
ISSN: 1477-3155
Popis: 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.
Databáze: OpenAIRE
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