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Abstract

Aptamers have recently emerged as reliable and promising targeting agents in the field of biology. However, their therapeutic potential has yet to be completely assessed due to their poor pharmacokinetics for systemic administration. Here, we describe a novel aptamer-antibody complex, designated an "oligobody" (oligomer+antibody) that may overcome the therapeutic limitations of aptamers. To provide proof-of-principle study, we investigated the druggability of oligobody in vivo using cotinine conjugated t44-OMe aptamer, which is specific for the sequence of pegaptanib, and an anti-cotinine antibody. The antibody part of oligobody resulted in extended in vivo pharmacokinetics of the aptamer without influencing its binding affinity. Moreover, the aptamer of oligobody penetrated deeply into the tumor tissues whereas the anti-VEGF antibody did not. Finally, the systemic administration of this oligobody reduced the tumor burden in a xenograft mouse model. Together, these results suggested that our oligobody strategy may represent a novel platform for rapid, low-cost and high-throughput cancer therapy. 

Author information

Heo K1, Min SW1, Sung HJ1, Kim HG1, Kim HJ1, Kim YH2, Choi BK1, Han S3, Chung S3, Lee ES2, Chung J4, Kim IH5.​

1Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.

2Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea; Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.

3School of Mechanical Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, Republic of Korea.

4Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Electronic address: junhochung@me.com.

5Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea; Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea. Electronic address: ikim@ncc.re.kr.