Abstract 1078: Identification of peptides binding to mesenchymal subtype breast cancer from phage display peptide library

Abstract

Most available therapeutic drugs efficiently treat tumors; however, absence of specificity has deleterious effects on patients. Identifying a tumor ablation method that has specificity with minimal to no side effects is needed. Phage display allows for expression of peptide and protein libraries on the surface of phage with a diversity of 109 peptides of different permutations, which leads to the selection of peptides and proteins, with high affinity and specificity. Phage display can be used as a tool to identify specific targets using a pIII phage library for identification of cell surface markers. To do so, we performed an initial depletion assay to isolate specific phages that express an affinity to human cells. We isolated a phage diversity of 10-2 from 109. Subsets of this population were used to identify phage and breast cancer cell interaction in vitro using an ELISA assay. Briefly, phages were exposed to epithelial and mesenchymal breast cancer cells and fibroblast cells. We have identified a phage profile that selectively targets tumor cells based on their transition from epithelial to mesenchymal. Interestingly, PE-26, a phage subset, indicated a greater affinity for more mesenchymal-like tumor cells. Moreover, we identified a 5-fold increase in the binding affinity for MDA-MB-231 and MCF-7 (overexpressed with TGF-β) in comparison to the control fibroblast cells. Additionally, PE-21 demonstrates a 6-fold increased affinity for breast cancer cells when contrasted with our control fibroblast cells. Our data provide further support that the identified phage profiles exhibit a preferential affinity for more mesenchymal-like tumor cells, which are known to be aggressive. This suggests their potential chemotherapeutic capability. Our future endeavors include further validation of selected phages and development of peptides to be employed as imaging agents to study EMT in vivo and as diagnostics to detect circulating tumor cells. Citation Format: Kelvin M. Jones, Rajeev Samant, Shree Singh, Deepa Bedi. Identification of peptides binding to mesenchymal subtype breast cancer from phage display peptide library [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 1078.