Peptidic tumor targeting agents: the road from phage display peptide selections to clinical applications

Abstract

Cancer has become the number one cause of death amongst Americans, killing approximately 1,600 people per day. Novel methods for early detection and the development of effective treatments are an eminent priority in medicine. For this reason, isolation of tumor-specific ligands is a growing area of research. Tumor-specific binding agents can be used to probe the tumor cell surface phenotype and to customize treatment accordingly by conjugating the appropriate cell-targeting ligand to an anticancer drug. This refines the molecular diagnosis of the tumor and creates guided drugs that can target the tumor while sparing healthy tissues. Additionally, these targeting agents can be used as in vivo imaging agents that allow for earlier detection of tumors and micrometastasis. Phage display is a powerful technique for the isolation of peptides that bind to a particular target with high affinity and specificity. The biopanning of intact cancer cells or tumors in animals can be used as the bait to isolate peptides that bind to cancer-specific cell surface biomarkers. Over the past 10 years, unbiased biopanning of phage-displayed peptide libraries has generated a suite of cancer targeting peptidic ligands. This review discusses the recent advances in the isolation of cancer-targeting peptides by unbiased biopanning methods and highlights the use of the isolated peptides in clinical applications.

Fig. (1)

Schematic for the unbiased selection of cancer-targeting peptides from phage displayed-peptide libraries. Cancer cells in culture or tumors within animals can be used as the bait for the biopanning. Amplification of eluted phage enriches for phage clones that bind the cell surface. Amplification of phage from the cell lysates enriches for peptide that mediate cellular uptake upon binding.

Scheme I

Convergent synthesis of tetrameric cell targeting peptides. Adapted from Li S, McGuire MJ, Lin M, Liu Y-H, Oyama T, Sun X, Brown KC. Mol Cancer Ther 2009; 8: 1239-1249.