Abstract LB-063: Phospholipid drug conjugates show specificity for a broad range of tumor cells and provides a novel approach for targeted or precision therapy

Abstract

The majority of anticancer drugs in clinical use have their utility limited by their toxicity to all proliferating cells, including normal cells and the inability to exert their effect on all of the tumor cells. Novel cytotoxic agents continue to be developed with unique mechanisms of action meant to provide increased targeting, however, many of these compounds still lack absolute tumor selectivity and continue to be limited in their therapeutic utilization due to off-target effects. Antibody drug conjugates (ADCs) have been design to bind to specific epitopes on the surface of tumor cells and have offered an alternative method to target tumor cells in an effort to reduce associated toxicities. Although highly selective, very few antibody drug conjugates are therapeutically useful since they only achieve modest cellular uptake and limited cell killing activity. Here we describe the development of a novel targeting platform using phospholipid ether (PLE) molecules to provide tumor cell specific targeting. These molecules known as phospholipid drug conjugates (PDCs) show high specificity for tumor cells; 6 to 30-fold increase in targeting tumor cells over normal tissue, result in up to 20% of exposed compound entering in to the tumor cells (as compared to < 1% of an ADC), and show a range of compounds can be conjugated to them. We have tested the uptake of our PDCs across over 80 different tumor cell lines and have shown consistent preferential uptake by tumor cells versus normal cells even when in co-culture. This could result in an improvement of the therapeutic index for many compounds. Citation Format: Jarrod Longcor, Maria Banach, Randall Hoover. Phospholipid drug conjugates show specificity for a broad range of tumor cells and provides a novel approach for targeted or precision therapy [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 LB-063.