Antibody-Assisted Delivery of a Peptide-Drug Conjugate for Targeted Cancer Therapy

Hyungjun Kim, Dobeen Hwang, Minsuk Choi, Soyoung Lee, Sukmo Kang, Yonghyun Lee, Sunghyun Kim, Junho Chung, Sangyong Jon

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


A number of cancer-targeting peptide-drug conjugates (PDCs) have been explored as alternatives to antibody-drug conjugates (ADCs) for targeted cancer therapy. However, the much shorter circulation half-life of PDCs compared with ADCs in vivo has limited their therapeutic value and thus their translation into the clinic, highlighting the need to develop new approaches for extending the half-life of PDCs. Here, we report a new strategy for targeted cancer therapy of a PDC based on a molecular hybrid between an antihapten antibody and a hapten-labeled PDC. An anticotinine antibody (Ab cot ) was used as a model antihapten antibody. The anticancer drug SN38 was linked to a cotinine-labeled aptide specific to extra domain B of fibronectin (cot-APT EDB ), yielding the model PDC, cot-APT EDB -SN38. The cotinine-labeled PDC showed specific binding to and cytotoxicity toward an EDB-overexpressing human glioblastoma cell line (U87MG) and also formed a hybrid complex (HC) with Ab cot in situ, designated HC[cot-APT EDB -SN38/Ab cot ]. In glioblastoma-bearing mice, in situ HC[cot-APT EDB -SN38/Ab cot ] significantly extended the circulation half-life of cot-APT EDB -SN38 in blood, and it enhanced accumulation and penetration within the tumor and, ultimately, inhibition of tumor growth. These findings suggest that the present platform holds promise as a new, targeted delivery strategy for PDCs in anticancer therapy.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalMolecular Pharmaceutics
Issue number1
StatePublished - 7 Jan 2019

Bibliographical note

Funding Information:
This work was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (Leading Researcher Program: NRF-2018R1A3B1052661).

Publisher Copyright:
Copyright © 2018 American Chemical Society.


  • SN38
  • anticotinine antibody
  • aptides
  • cancer therapy
  • extra domain B of fibronectin
  • peptide-drug conjugates


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