Trends in Glycoscience and Glycotechnology
Online ISSN : 1883-2113
Print ISSN : 0915-7352
ISSN-L : 0915-7352
MINIREVIEW
Development of Lectin–Drug Conjugates for Elimination of Undifferentiated Cells and Cancer Therapy
Hiroaki Tateno
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2019 Volume 31 Issue 183 Pages E121-E127

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Abstract

We previously analyzed the cell-surface glycans of human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) using lectin microarrays and mass spectrometry. We demonstrated that H type3 (Fucα1-2Galβ1-3GalNAc) is highly expressed in hESCs/hiPSCs compared with human somatic cells. Furthermore, we generated a lectin–drug conjugate (LDC) by fusing rBC2LCN with Pseudomonas aeruginosa exotoxin A as a cytotoxic agent for the selective elimination of hESCs/hiPSCs. Recently, we found that rBC2LCN strongly binds to a pancreatic cancer cell line Capan-1 with the cancer stem cell like property. rBC2LCN stained all of the pancreatic ductal adenocarcinoma (PDAC) tissues obtained from 69 patients. We therefore perceived LDC as a potential anticancer drug. The half maximal effective concentration (EC50) of LDC to Capan-1 was 1.04 pg/mL (0.0195 pM), which was 1,000-fold lower than that reported for conventional immunotoxins. Furthermore, the intraperitoneal or intravenous administration of LDC reduced the tumor weight in orthotopic and peritoneal dissemination mouse models. In this review, the development of LDC as a novel modality and its application to pancreatic cancer therapy are mainly described.

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© 2019 FCCA (Forum: Carbohydrates Coming of Age)
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