Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment

Sun Il Choi; Yu Sun Lee; Yul Min Lee; Hyun Jung Kim; Won Jong Kim; Sungjin Jung; Ji Eun Im; Mi Rim Lee; Joon Ki Kim; A. Ra Jeon; Sang Myung Woo; Goo Taeg Oh; Kyun Heo; Yun Hee Kim; In Hoo Kim

doi:10.1016/j.jconrel.2023.03.048

Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment

Sun Il Choi, Yu Sun Lee, Yul Min Lee, Hyun Jung Kim, Won Jong Kim, Sungjin Jung, Ji Eun Im, Mi Rim Lee, Joon Ki Kim, A. Ra Jeon, Sang Myung Woo, Goo Taeg Oh, Kyun Heo, Yun Hee Kim, In Hoo Kim

Life Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Owing to a lack of reliable markers and therapeutic targets, pancreatic ductal adenocarcinoma (PDAC) remains the most lethal malignant tumor despite numerous therapeutic advances. In this study, we utilized cell-SELEX to isolate a DNA aptamer recognizing the natural conformation of the target on the cell surface. PAp7T8, an aptamer optimized by size and chemical modification, exhibited specific targeting to pancreatic cancer cells and orthotopic xenograft pancreatic tumors. To confer therapeutic functions to the aptamer, we adopted a drug-conjugated oligobody (DOligobody) strategy. Monomethyl auristatin E was used as a cytotoxic drug, digoxigenin acted as a hapten, and the humanized anti-digoxigenin antibody served as a universal carrier of the aptamer. The resulting PAp7T8-DOligobody showed extended in vivo half-life and markedly inhibited tumor growth in an orthotopic pancreatic cancer xenograft model without causing significant toxicity. Therefore, PAp7T8-DOligobody represents a promising novel therapeutic delivery platform for PDAC.

Original language	English
Pages (from-to)	940-952
Number of pages	13
Journal	Journal of Controlled Release
Volume	360
DOIs	https://doi.org/10.1016/j.jconrel.2023.03.048
State	Published - Aug 2023

Keywords

Aptamer
Drug delivery
Oligobody
Pancreatic ductal adenocarcinoma
Targeted therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jconrel.2023.03.048

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Choi, S. I., Lee, Y. S., Lee, Y. M., Kim, H. J., Kim, W. J., Jung, S., Im, J. E., Lee, M. R., Kim, J. K., Jeon, A. R., Woo, S. M., Oh, G. T., Heo, K., Kim, Y. H., & Kim, I. H. (2023). Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment. Journal of Controlled Release, 360, 940-952. https://doi.org/10.1016/j.jconrel.2023.03.048

@article{0d676050bb004adfbfb3d775d123e226,

title = "Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment",

abstract = "Owing to a lack of reliable markers and therapeutic targets, pancreatic ductal adenocarcinoma (PDAC) remains the most lethal malignant tumor despite numerous therapeutic advances. In this study, we utilized cell-SELEX to isolate a DNA aptamer recognizing the natural conformation of the target on the cell surface. PAp7T8, an aptamer optimized by size and chemical modification, exhibited specific targeting to pancreatic cancer cells and orthotopic xenograft pancreatic tumors. To confer therapeutic functions to the aptamer, we adopted a drug-conjugated oligobody (DOligobody) strategy. Monomethyl auristatin E was used as a cytotoxic drug, digoxigenin acted as a hapten, and the humanized anti-digoxigenin antibody served as a universal carrier of the aptamer. The resulting PAp7T8-DOligobody showed extended in vivo half-life and markedly inhibited tumor growth in an orthotopic pancreatic cancer xenograft model without causing significant toxicity. Therefore, PAp7T8-DOligobody represents a promising novel therapeutic delivery platform for PDAC.",

keywords = "Aptamer, Drug delivery, Oligobody, Pancreatic ductal adenocarcinoma, Targeted therapy",

author = "Choi, {Sun Il} and Lee, {Yu Sun} and Lee, {Yul Min} and Kim, {Hyun Jung} and Kim, {Won Jong} and Sungjin Jung and Im, {Ji Eun} and Lee, {Mi Rim} and Kim, {Joon Ki} and Jeon, {A. Ra} and Woo, {Sang Myung} and Oh, {Goo Taeg} and Kyun Heo and Kim, {Yun Hee} and Kim, {In Hoo}",

note = "Funding Information: This work was supported by the Research Core Center in National Cancer Center Korea . This study was supported by the Korea Technology and Information Promotion Agency for Small and Medium Enterprises [grant number: S2562351 ], National Cancer Center [grant number: NCC-1410270 & NCC-2310632 ], and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning [grant number: NRF-2019R1A2C1010919 ]. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The figures were created with BioRender.com . Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

doi = "10.1016/j.jconrel.2023.03.048",

language = "English",

volume = "360",

pages = "940--952",

journal = "Journal of Controlled Release",

issn = "0168-3659",

publisher = "Elsevier",

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TY - JOUR

T1 - Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment

AU - Choi, Sun Il

AU - Lee, Yu Sun

AU - Lee, Yul Min

AU - Kim, Hyun Jung

AU - Kim, Won Jong

AU - Jung, Sungjin

AU - Im, Ji Eun

AU - Lee, Mi Rim

AU - Kim, Joon Ki

AU - Jeon, A. Ra

AU - Woo, Sang Myung

AU - Oh, Goo Taeg

AU - Heo, Kyun

AU - Kim, Yun Hee

AU - Kim, In Hoo

N1 - Funding Information: This work was supported by the Research Core Center in National Cancer Center Korea . This study was supported by the Korea Technology and Information Promotion Agency for Small and Medium Enterprises [grant number: S2562351 ], National Cancer Center [grant number: NCC-1410270 & NCC-2310632 ], and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning [grant number: NRF-2019R1A2C1010919 ]. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The figures were created with BioRender.com . Publisher Copyright: © 2023 The Authors

PY - 2023/8

Y1 - 2023/8

N2 - Owing to a lack of reliable markers and therapeutic targets, pancreatic ductal adenocarcinoma (PDAC) remains the most lethal malignant tumor despite numerous therapeutic advances. In this study, we utilized cell-SELEX to isolate a DNA aptamer recognizing the natural conformation of the target on the cell surface. PAp7T8, an aptamer optimized by size and chemical modification, exhibited specific targeting to pancreatic cancer cells and orthotopic xenograft pancreatic tumors. To confer therapeutic functions to the aptamer, we adopted a drug-conjugated oligobody (DOligobody) strategy. Monomethyl auristatin E was used as a cytotoxic drug, digoxigenin acted as a hapten, and the humanized anti-digoxigenin antibody served as a universal carrier of the aptamer. The resulting PAp7T8-DOligobody showed extended in vivo half-life and markedly inhibited tumor growth in an orthotopic pancreatic cancer xenograft model without causing significant toxicity. Therefore, PAp7T8-DOligobody represents a promising novel therapeutic delivery platform for PDAC.

AB - Owing to a lack of reliable markers and therapeutic targets, pancreatic ductal adenocarcinoma (PDAC) remains the most lethal malignant tumor despite numerous therapeutic advances. In this study, we utilized cell-SELEX to isolate a DNA aptamer recognizing the natural conformation of the target on the cell surface. PAp7T8, an aptamer optimized by size and chemical modification, exhibited specific targeting to pancreatic cancer cells and orthotopic xenograft pancreatic tumors. To confer therapeutic functions to the aptamer, we adopted a drug-conjugated oligobody (DOligobody) strategy. Monomethyl auristatin E was used as a cytotoxic drug, digoxigenin acted as a hapten, and the humanized anti-digoxigenin antibody served as a universal carrier of the aptamer. The resulting PAp7T8-DOligobody showed extended in vivo half-life and markedly inhibited tumor growth in an orthotopic pancreatic cancer xenograft model without causing significant toxicity. Therefore, PAp7T8-DOligobody represents a promising novel therapeutic delivery platform for PDAC.

KW - Aptamer

KW - Drug delivery

KW - Oligobody

KW - Pancreatic ductal adenocarcinoma

KW - Targeted therapy

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U2 - 10.1016/j.jconrel.2023.03.048

DO - 10.1016/j.jconrel.2023.03.048

M3 - Article

C2 - 37001565

AN - SCOPUS:85153272410

SN - 0168-3659

VL - 360

SP - 940

EP - 952

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment

Abstract

Keywords

UN SDGs

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