An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies

Kyun Heo, Sung Won Min, Ho Jin Sung, Han Gyul Kim, Hyun Jung Kim, Yun Hee Kim, Beom Kyu Choi, Sewoon Han, Seok Chung, Eun Sook Lee, Junho Chung, In Hoo Kim

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalJournal of Controlled Release
Volume229
DOIs
Publication statusPublished - 2016 May 10

Fingerprint

Cotinine
Antibodies
Anti-Idiotypic Antibodies
Pharmacokinetics
Neoplasms
Tumor Burden
Heterografts
Vascular Endothelial Growth Factor A
Therapeutics
Costs and Cost Analysis
pegaptanib

Keywords

  • Antibody
  • Aptamer
  • Cotinine
  • Oligobody
  • Targeted cancer therapy

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies. / Heo, Kyun; Min, Sung Won; Sung, Ho Jin; Kim, Han Gyul; Kim, Hyun Jung; Kim, Yun Hee; Choi, Beom Kyu; Han, Sewoon; Chung, Seok; Lee, Eun Sook; Chung, Junho; Kim, In Hoo.

In: Journal of Controlled Release, Vol. 229, 10.05.2016, p. 1-9.

Research output: Contribution to journalArticle

Heo, K, Min, SW, Sung, HJ, Kim, HG, Kim, HJ, Kim, YH, Choi, BK, Han, S, Chung, S, Lee, ES, Chung, J & Kim, IH 2016, 'An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies', Journal of Controlled Release, vol. 229, pp. 1-9. https://doi.org/10.1016/j.jconrel.2016.03.006
Heo, Kyun ; Min, Sung Won ; Sung, Ho Jin ; Kim, Han Gyul ; Kim, Hyun Jung ; Kim, Yun Hee ; Choi, Beom Kyu ; Han, Sewoon ; Chung, Seok ; Lee, Eun Sook ; Chung, Junho ; Kim, In Hoo. / An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies. In: Journal of Controlled Release. 2016 ; Vol. 229. pp. 1-9.
@article{90ce9e544a0847728d87a63c27861633,
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.",
keywords = "Antibody, Aptamer, Cotinine, Oligobody, Targeted cancer therapy",
author = "Kyun Heo and Min, {Sung Won} and Sung, {Ho Jin} and Kim, {Han Gyul} and Kim, {Hyun Jung} and Kim, {Yun Hee} and Choi, {Beom Kyu} and Sewoon Han and Seok Chung and Lee, {Eun Sook} and Junho Chung and Kim, {In Hoo}",
year = "2016",
month = "5",
day = "10",
doi = "10.1016/j.jconrel.2016.03.006",
language = "English",
volume = "229",
pages = "1--9",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

TY - JOUR

T1 - An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies

AU - Heo, Kyun

AU - Min, Sung Won

AU - Sung, Ho Jin

AU - Kim, Han Gyul

AU - Kim, Hyun Jung

AU - Kim, Yun Hee

AU - Choi, Beom Kyu

AU - Han, Sewoon

AU - Chung, Seok

AU - Lee, Eun Sook

AU - Chung, Junho

AU - Kim, In Hoo

PY - 2016/5/10

Y1 - 2016/5/10

N2 - 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.

AB - 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.

KW - Antibody

KW - Aptamer

KW - Cotinine

KW - Oligobody

KW - Targeted cancer therapy

UR - http://www.scopus.com/inward/record.url?scp=84962596774&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962596774&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2016.03.006

DO - 10.1016/j.jconrel.2016.03.006

M3 - Article

VL - 229

SP - 1

EP - 9

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -