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Therapeutic Application of Drug-Conjugated HER2 Oligobody (HER2-DOligobody)
- Therapeutic Application of Drug-Conjugated HER2 Oligobody (HER2-DOligobody)
- Kim, Hyun Jung; Sung, Ho Jin; Lee, Yul Min; Choi, Sun Il; Kim, Yun-Hee; Heo, Kyun; Kim, In-Hoo
- Ewha Authors
- Issue Date
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol. 21, no. 9
- aptamer; antibody-drug conjugate (ADC); oligobody; drug-conjugated oligobody (DOligobody); HER2; cancer therapeutics
- SCIE; SCOPUS
- Document Type
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- 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.
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