MRNA Display Discovery of a Novel Programmed Death Ligand 1 (PD-L1) Binding Peptide (a Peptide Ligand for PD-L1)

Golnaz Kamalinia, Brian Joseph Engel, Anupallavi Srinivasamani, Brian J. Grindel, Justin N. Ong, Michael A. Curran, Terry T. Takahashi, Steven W. Millward, Richard W. Roberts, Richard W. Roberts, Richard W. Roberts

Research output: Contribution to journalArticlepeer-review

Abstract

Programmed death ligand 1 (PD-L1) is a critical immune checkpoint ligand whose overexpression on tumor cells provides a mechanism of escape from immune surveillance. The interaction between PD-L1 and PD-1 on T cell lymphocytes suppresses both T cell activation and effector function and is engaged by cancers to dampen antitumor immunity. Here, we used mRNA display to engineer an 18-residue linear peptide that binds to human PD-L1. This peptide, which we term SPAM (signal peptide-based affinity maturated ligand), is nonhomologous to known PD-L1 binding peptides and mAbs, with dissociation constants (KD) of 119 and 67 nM for unglycosylated and glycosylated human PD-L1, respectively. The SPAM peptide is highly selective for human PD-L1 and shows no significant binding to either mouse PD-L1 or human PD-L2. Competition binding assays indicate that the SPAM peptide binding site overlaps with the binding site of PD-1 as well as therapeutic anti-PD-L1 antibodies. Taken together, these results suggest that the SPAM peptide specifically binds to human PD-L1 and could potentially serve as a PD-L1 affinity agent and PD-L1/PD-1 pathway modulator.

Original languageEnglish (US)
Pages (from-to)1630-1641
Number of pages12
JournalACS Chemical Biology
Volume15
Issue number6
DOIs
StatePublished - Jun 19 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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