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.

journal_name

Int J Mol Sci

authors

Kim HJ,Sung HJ,Lee YM,Choi SI,Kim YH,Heo K,Kim IH

doi

10.3390/ijms21093286

subject

Has Abstract

pub_date

2020-05-06 00:00:00

issue

9

issn

1422-0067

pii

ijms21093286

journal_volume

21

pub_type

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