Abstract A103: Identification and functional analysis of CLIC1(Chloride intracellular channel protein1)-binding peptide

Abstract Targeted therapy is medication that selectively destroys cancer cells using small-molecule drugs or antibodies. Currently, cancer drugs which we commonly use are chemotherapeutic agents but targeted therapy which treats only certain cancer cells is being studied because it causes less side effects on normal cells. Compared to antibodies, peptides can be used as a targeting ligand because they are relatively small, have high tissue penetration ability, and lower immunogenicity. Chloride intracellular channel protein1 (CLIC1) is a metamorphic protein as it can exist in two forms: soluble globular protein or transmembrane protein. CLIC1 is related to cancer angiogenesis, cell migration and metastasis and is upregulated in various types of cancer, including hepatocellular carcinoma, lung cancer, colon cancer, glioblastoma stem cells, presenting it as a promising therapeutic cancer target. In this study, we identified a peptide candidate (named CLIC1pep) that bind to CLIC1 using phage display. Peptide specific binding was confirmed through ELISA, and pull-down assays. CLIC1pep showed a high binding affinity to CLIC1 protein. CLIC1pep was conjugated with a cell-penetrating peptide (R7) to increase its cell penetration (R7-CLIC1pep). We found that R7-CLIC1pep did not induce cancer cell death, but it penetrated and bound to CLIC1 in the cytoplasm. Also, R7-CLIC1pep inhibited the membrane insertion of CLIC1 in the cytoplasm and reduced the migration and invasion of cancer cells through reducing the p-ERK levels. As a future direction, we plan to design the CLIC1pep-based ProTAC to degrade CLIC1 in cells and examine its potential as an effective anti-cancer therapeutic agent. Citation Format: Aryeong Lee, Byungheon Lee. Identification and functional analysis of CLIC1(Chloride intracellular channel protein1)-binding peptide [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A103.