Abstract A029: Identification of cancer-specific CPP from human telomerase peptide library and its drug delivery potential in anti-cancer strategy

Abstract

Abstract A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide has been identified as a cell-penetrating peptide (CPP) in our previous study. This hTERT derived CPP was delivered into a variety of cells including various cancer cell lines and primary blood cells. Moreover, the CPP was predominantly located in the cytoplasm of the cells, while a significantly higher proportion of TAT peptide was localized in the nucleus. In order to reduce adverse non-specific toxic side effects of current anticancer drug, we developed cancer-specific anticancer drug delivery system using hTERT derived CPP. The cell penetrating activity was Pep 98, a specific hTERT derived CPP, was evaluated in head and neck cancer cells. The permeability of specific telomerase derived Pep 98-FITC into cancer cells was 20-300 fold higher than control peptide groups in head and neck cancer cells. These result suggest that pep98 can be used to reduce the side effects and increase the efficacy of cancer therapy through the use of specific anticancer drug delivery system.We conjugated Pep 98 with STAT 3 inhibitor (NSC74859) which has been presented as a molecular therapeutic target for head and neck cancer and evaluated concentration of NSC74589 for anti-cancer activity in head and neck cancer cell line. The result showed that the concentration of Pep-98 conjugated NSC74589 could be reduced up to 1/10-20 dose level compared with NSC74589 alone in head and neck cancer cells. Pep 98-NSC74859 conjugates were found to be capable of specific killing head and neck cancer cells without affecting normal fibroblast cells.We have confirmed the possibility of developing a new head neck cancer anticancer drug with improved therapeutic efficacy through the conjugation of the STAT3 inhibitor with hTERT derived peptide. Citation Format: Yoon Seon Lee, Myung Jin Lee, Won Jun Shon. Identification of cancer-specific CPP from human telomerase peptide library and its drug delivery potential in anti-cancer strategy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A029.