Authors: T.I. Samoylova, N.E. Morrison, N.R. Cox
Affilation: Auburn University, United States
Pages: 434 - 437
Keywords: phage probes, patient-specific, cancer, glioma
Phage display is a powerful discovery tool with a variety of applications including identification of peptides that specifically recognize and bind to cell-surface targets. Phage particles carrying such peptides have the potential to serve as nanoprobes for profiling of cancer cell surfaces, allowing parallel development of diagnostics with companion therapeutics. We tested phage probes derived from a landscape phage display library for different glioma cell lines. Four phage clones displaying glioma-selective peptides were assayed for binding to human glioma cell lines, each with a different morphology and derived from a different patient. These phage clones were bound to the cells in distinctive patterns that were individual for each cell line. Subsequently, we designed and tested anti-cancer peptides with two domains: (1) glioma-binding for selective delivery to cancer cells and (2) pro-apoptotic for cell killing. The resulting bifunctional peptides showed preferential cytotoxicity toward glioma cells compared to normal brain astrocytes. The cytotoxic effects on glioma cells were dose-dependent and exceeded significantly the effects of the pro-apoptotic peptide alone. A strategy that incorporates the use of phage nanoprobes for cell-surface molecular profiling of individual tumors followed by cytotoxic treatments formulated on the basis of tumor profiles is discussed.