title: An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies.
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.
authors.affiliation: Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.
authors.forename: Kyun
authors.initials: K
authors.lastname: Heo
authors.affiliation: Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Min
authors.affiliation: Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Sung
authors.affiliation: Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.
authors.forename: Han Gyul
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Research 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.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.
authors.forename: Beom Kyu
authors.initials: BK
authors.lastname: Choi
authors.affiliation: School of Mechanical Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, Republic of Korea.
authors.forename: Sewoon
authors.initials: S
authors.lastname: Han
authors.affiliation: School of Mechanical Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, Republic of Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Chung
authors.affiliation: Research 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.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Electronic address: junhochung@me.com.
authors.forename: Junho
authors.initials: J
authors.lastname: Chung
authors.affiliation: Research 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.
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000493:pharmacokinetics / Q000627:therapeutic use; D003367:Cotinine / Q000737:chemistry / Q000276:immunology; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D042461:Vascular Endothelial Growth Factor A; C495058:pegaptanib; D003367:Cotinine
keywords: Antibody; Aptamer; Cotinine; Oligobody; Targeted cancer therapy