Abstract 1853: BIK-E715E, an integrin-targeting ligand-drug conjugate equipped with a novel drug delivery system, demonstrates enhanced antitumor efficacy in glioblastoma

We developed a novel drug delivery system ELiTE-DDS, designed to enhance target-selective intracellular delivery of therapeutic agents, where ELiTE stands for enhancing ligand targeting and endocytosis. Integrins αvβ3 and αvβ5, highly expressed in glioblastoma tumor cells, are molecular targets for glioblastoma treatment. In this study, we applied the ELiTE-DDS platform to a conjugate consisting of a high-affinity integrin αvβ3/αvβ5-binding ligand, D-[c(RGDfK)]2, and a topoisomerase I inhibitor exatecan, yielding BIK-E715E as a drug candidate for glioblastoma. BIK-E715E exhibited high selectivity and binding affinities for integrins αvβ3 and αvβ5 and was internalized through an Arf6-dependent, dynamin-independent endocytic pathway. Cellular treatment with BIK-E715E produced PARP cleavage and phosphorylation of Chk1 and histone H2AX, indicating drug-induced apoptosis and DNA damage, respectively. There was significant translocation of BIK-E715E in a hCMEC/D3 in vitro blood-brain barrier (BBB) model, suggesting its receptor-mediated transcytosis across the BBB. In U87MG subcutaneous and orthotopic xenograft mouse models, BIK-E715E accumulated in tumors with high efficiency and resulted in marked inhibition of tumor growth, which was greater than exatecan-induced growth inhibition. These data demonstrate that BIK-E715E is an attractive drug candidate for glioblastoma, equipped with a novel drug delivery system. Further, they also suggest that our ELiTE-DDS platform has great potential for enhancing target-selective intracellular delivery of therapeutic agents across the BBB. Citation Format: Kideok Shin, Hyunju Sung, Jae Ho Jung, Sang Eun Kim. BIK-E715E, an integrin-targeting ligand-drug conjugate equipped with a novel drug delivery system, demonstrates enhanced antitumor efficacy in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1853.