Directed Evolution of PD-L1-Targeted Affibodies by mRNA Display

Authors

Brian J Grindel
Brian J Engel
Justin N Ong
Anupallavi Srinivasamani
Xiaowen Liang
Niki M Zacharias
Robert C Bast
Michael A Curran
Terry T Takahashi
Richard W Roberts
Steven W Millward

Publication Date

6-17-2022

Journal

ACS Chemical Biology

Abstract

Therapeutic monoclonal antibodies directed against PD-L1 (e.g., atezolizumab) disrupt PD-L1:PD-1 signaling and reactivate exhausted cytotoxic T-cells in the tumor compartment. Although anti-PD-L1 antibodies are successful as immune checkpoint inhibitor (ICI) therapeutics, there is still a pressing need to develop high-affinity, low-molecular-weight ligands for molecular imaging and diagnostic applications. Affibodies are small polypeptides (∼60 amino acids) that provide a stable molecular scaffold from which to evolve high-affinity ligands. Despite its proven utility in the development of imaging probes, this scaffold has never been optimized for use in mRNA display, a powerful

Keywords

Amino Acids, Animals, B7-H1 Antigen, Ligands, Mice, Neoplasms, Programmed Cell Death 1 Receptor, RNA, Messenger

DOI

10.1021/acschembio.2c00218

PMID

35611948

PMCID

PMC10691555

PubMedCentral® Posted Date

12-1-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes