Phage display screening of therapeutic peptide for cancer targeting and therapy

Phei Er Saw,Er-Wei Song

doi:10.1007/s13238-019-0639-7

Phei Er Saw, Er-Wei Song

Open Access

https://doi.org/10.1007/s13238-019-0639-7

Copy DOI

Abstract

ABSTRACTRecently, phage display technology has been announced as the recipient of Nobel Prize in Chemistry 2018. Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched through the biopanning process; proving to be a powerful technique in the screening of peptide with high affinity and selectivity. In this review, we will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ, in vitro, in vivo, and ex vivo screening methods. We will then discuss prominent examples of solid tumor targeting-peptides; namely peptide targeting tumor vasculature, tumor microenvironment (TME) and over-expressed receptors on cancer cells identified through phage display screening. We will also discuss the current challenges and future outlook for targeting peptide-based therapeutics in the clinics.

Highlights

Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched through the biopanning process; proving to be a powerful technique in the screening of peptide with high affinity and selectivity
We will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ, in vitro, in vivo, and ex vivo screening methods
We will discuss prominent examples of solid tumor targeting-peptides; namely peptide targeting tumor vasculature, tumor microenvironment (TME) and overexpressed receptors on cancer cells identified through phage display screening

Summary

INTRODUCTION

Peptides are 2-dimensional, linear chains of amino acids, which are usually short (less than 50 AA) in length (Hayashi et al, 2012) They are either designed by rational computing methods or phage display screening to obtain peptides that binds with high specificity to the target of interest, with a possibility of modulating the target (Marqus et al, 2017). We will review the utilization of phage display biopanning with modifications gearing towards in situ, in vitro, in vivo, ex vivo and in human application for high affinity peptide screening. Phage-display is a powerful technology for screening and isolating target specific peptides. This method utilizes bacteriophage to display foreign peptides or antibodies on their surface through insertion of the gene encoding the corresponding polypeptides into the phage genome. The target is artificially coated onto the plate, which could be misrepresent the actual secondary structure of the target in a living system, increases the risk of isolating a peptide that only binds to the receptor in this particular setting (Kim et al, 2012b)

G Pick colonies and grow large quantity of phages F

Findings

COMPLIANCE WITH ETHICS GUIDELINES