Antibody drug conjugates (ADCs), consisting of a cancer-specific antibody and cytotoxic\npayload, are shown to be a potent class of anticancer therapeutics, with enhanced therapeutic effcacy\nand reduced â??off-targetâ? side effects. However, the therapeutic window of ADCs is narrowed by\nproblems such as diffculty in site-specific conjugation of payload, changes in antibody stability\ndue to payload conjugation, and diffculty in tissue penetration. In this respect, aptamers have\nadvantages in drug-delivery, as they can be easily and stably conjugated with cytotoxic drugs. We\npreviously reported that oligobody, an aptamer-antibody complex, is a novel delivery method for\naptamer-based therapeutics. In the current study, we describe DOligobody, a drug-conjugated\noligobody comprising an aptamer-drug conjugate and an antibody. A cotinine-conjugated anti-HER2\naptamer (cot-HER2apt) was specifically bound to HER2-positive NCI-N87 cells, and underwent\nreceptor-mediated endocytosis. Further, HER2-DOligobody, a cot-HER2apt-conjugated monomethyl\nauristatin E (cot-HER2apt-MMAE) oligobody, inhibited the growth of HER2-positive NCI-N87 cells.\nFinally, systemic administration of HER2-DOligobody significantly reduced tumor growth in a\nxenograft mouse model. Taken together, these results suggest that our DOligobody strategy may be a\npowerful platform for rapid, low-cost and effective cancer therapy.
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