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International Journal of Molecular Sciences
Article . 2020 . Peer-reviewed
License: CC BY
Data sources: Crossref
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PubMed Central
Other literature type . 2020
Data sources: PubMed Central
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Therapeutic Application of Drug-Conjugated HER2 Oligobody (HER2-DOligobody)

Authors: Hyun Jung Kim; Ho Jin Sung; Yul Min Lee; Sun Il Choi; Yun-Hee Kim; Kyun Heo; In-Hoo Kim;

Therapeutic Application of Drug-Conjugated HER2 Oligobody (HER2-DOligobody)

Abstract

Antibody drug conjugates (ADCs), consisting of a cancer-specific antibody and cytotoxic payload, are shown to be a potent class of anticancer therapeutics, with enhanced therapeutic efficacy and reduced “off-target” side effects. However, the therapeutic window of ADCs is narrowed by problems such as difficulty in site-specific conjugation of payload, changes in antibody stability due to payload conjugation, and difficulty in tissue penetration. In this respect, aptamers have advantages in drug-delivery, as they can be easily and stably conjugated with cytotoxic drugs. We previously reported that oligobody, an aptamer-antibody complex, is a novel delivery method for aptamer-based therapeutics. In the current study, we describe DOligobody, a drug-conjugated oligobody comprising an aptamer-drug conjugate and an antibody. A cotinine-conjugated anti-HER2 aptamer (cot-HER2apt) was specifically bound to HER2-positive NCI-N87 cells, and underwent receptor-mediated endocytosis. Further, HER2-DOligobody, a cot-HER2apt-conjugated monomethyl auristatin E (cot-HER2apt-MMAE) oligobody, inhibited the growth of HER2-positive NCI-N87 cells. Finally, systemic administration of HER2-DOligobody significantly reduced tumor growth in a xenograft mouse model. Taken together, these results suggest that our DOligobody strategy may be a powerful platform for rapid, low-cost and effective cancer therapy.

Keywords

Immunoconjugates, Receptor, ErbB-2, Mice, Nude, Article, cancer therapeutics, Mice, HER2, Cell Line, Tumor, oligobody, Animals, Humans, Cotinine, Cell Proliferation, Mice, Inbred BALB C, aptamer, drug-conjugated oligobody (DOligobody), Antibodies, Monoclonal, Mammary Neoplasms, Experimental, Endocytosis, antibody-drug conjugate (ADC), Female, Oligopeptides, Aptamers, Peptide

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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
8
Top 10%
Average
Average
Green
gold