Abstract 5772: Engineered lectins to treat cancer

Abstract

Abstract Targeted delivery of cytotoxic compounds to tumors has become one of the most dynamic areas of research and development in the cancer therapy field. In this context, glycosphingolipids (GSLs) represent a promising class of tumor markers. Indeed, cancer patients have altered GSL expression patterns on their tumoral cells compared to healthy tissue (Krengel et al., 2014). In a recent prioritization of cancer antigens by the National Cancer Institute at Rockville (USA), 4 out of 75 were GSLs (GD2, GD3, fucosyl-GM1, and GM3), with GD2 arriving already at the 12th position (Cheever et al., 2009). However, GSLs are only rarely addressed in the context of tumor targeting, obtaining GSL specific antibodies being a notorious difficult task. An exception is the anti-GD2 antibody, dinutuximab, which entered the market for the treatment of high-risk neuroblastoma patients, which is unfortunately associated to dose-limiting acute toxicity (Yu et al., 2010). This project aims at developing a novel class of therapeutic products for the delivery of therapeutic compounds by targeting tumor-specific GSLs. Our products are based on a naturally occurring GSL-binding lectin with intrinsic tumor targeting capacity. We will rely on a proprietary technology to derive products which are tuned to transport cytotoxic compounds specifically into cancer cells. As a proof of concept, we apply our technology to a tumor-specific GSL, GD2, to generate a therapeutic formulation against neuroblastoma, one of the most frequent cancer in children under 5 years old. Our technology has truly groundbreaking potential as, in principle, it can apply to any GSL to specifically target several common tumors. Citation Format: Thomas Murarasu, Ludger Johannes. Engineered lectins to treat cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5772.