
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.
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
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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