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J. Control. Release, Available online 6 April 2023 | https://doi.org/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 ^a,b,c, Yu-Sun Lee ^a,d, Yul Min Lee ^a,e, Hyun Jung Kim ^a,f, Won Jong Kim ^g,h, Sungjin Jung ^h, Ji Eun Im ^a, Mi Rim Lee ^a,i, Joon Ki Kim ^a, A-Ra Jeon ^a, Sang Myung Woo ^a,i,j, Goo Taeg Oh ^c, Kyun Heo ^f, Yun-Hee Kim ^a,i,1, In-Hoo Kimⁱ

^aResearch Institute, National Cancer Center, Goyang 10408, Republic of Korea
^bHenan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, Henan 475004, China
^cDepartment of Life Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
^dDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
^eJP Bio A Co., Seongnam 13606, Republic of Korea
^fBiopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul 02707, Republic of Korea
^gDepartment of Chemistry, POSTECH-Catholic Biomedical Engineering Institute, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
^hSchool of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
ⁱGraduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea
^jCenter for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Republic of Korea

¹Lead contact
Corresponding authors : Kyun Heo, Yun-Hee Kim

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.

논문정보

형식Research article
게재일2023년 04월 (BRIC 등록일 2023-04-28)
연구진국내(교신)+국외 연구진
분야 생명과학 > 노화/암생물학

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