Abstract 1863: A cytotoxic peptide designed for tumor-targeted delivery of co-injected molecules

Abstract Clinical trials have highlighted its promise as a tumor-targeted delivery system and enhancer of anti-cancer therapies. In this study, we developed and analyzed an iRGD, tumor specific homing peptide, conjugate linked to monomethyl auristatin F (MMAF), a highly potent antimitotic agent. This conjugate demonstrated dual functionality as a tumor-targeted cytotoxic agent and a delivery platform for co-administered drugs. The iRGD-MMAF conjugate selectively internalized and killed tumor cells in vitro through αv integrin-dependent pathways. In vivo, systemic injection of iRGD-MMAF resulted in tumor-specific localization and widespread distribution within the extravascular tumor tissue, consistent with iRGD’s tumor-penetrating properties. Additionally, iRGD-MMAF significantly improved tumor-specific uptake of a co-injected drug, confirming its efficacy as a delivery scaffold. These findings suggest that chemically modified iRGD peptides with added therapeutic properties maintain their ability to enhance co-administered drug delivery to tumors. Citation Format: Norio Miyamura, Chisato M. Yamazaki, Kyoji Tsuchikama, Kazuki N. Sugahara. A cytotoxic peptide designed for tumor-targeted delivery of co-injected molecules [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 1863.