Abstract 3120: Application of a lectin as a drug carrier for glycan-targeting cancer therapy

Various cancers such as pancreatic ductal adenocarcinoma (PDAC) remain intractable despite recent advances in tumour-targeting antibody drugs. Although the outermost coating of every cell type is predominantly composed of cell-specific glycans, antibody strategies have hit walls of technical difficulties in intentional glycan targeting, and medico-economic burden. Lectins, proteins with glycan-binding potential, could be used as an alternative scaffold; however, the prejudice that all lectins mediate harmful haemagglutination limited its use only in experimental and diagnostic applications. Here, we show the successful in vivo application of a lectin as a drug carrier for cancer therapy. We have employed rBC2LC-N lectin since this has already shown a specific affinity between PDAC cell-surface glycans. When a lectin-drug conjugate (LecD) was developed by fusion with a bacterial exotoxin, the 50% inhibitory concentration (1.04 pg/ml=0.0195 pM) was 1000 times lower than that of conventional immunotoxins (on the order of ng/ml). In addition, we have revealed that rBC2LC-N lectin was safely administrable to mice without haemagglutination. Administration of this LecD in a PDAC mouse model of subcutaneous nodules and peritoneal dissemination, generated prominent therapeutic effects. The utilization of lectins as an in vivo drug-carrier targeting cancer glycan shows realistic potential when paired with advanced lectin engineering technologies, and their applications could be expanded by coupling with small molecule and/or nanoparticle drugs. Citation Format: Tatsuya Oda, Osamu Shimomura, Hiroaki Tateno, Jun Hirabayashi, Masayuki Noguchi, Shigeru Chiba, Makoto Asashima, Nobuhiro Ohkohchi. Application of a lectin as a drug carrier for glycan-targeting cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3120. doi:10.1158/1538-7445.AM2017-3120