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, Sung‐Jin 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
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.