PXD020918

PXD020918 is an original dataset announced via ProteomeXchange.

Title	Peptide ‘Nano-Spiderwebs’ for Cancer Immunotherapy: New Receptor-Engineered Supramolecular Antagonists to PD-L1
Description	Immunol checkpoint blockade therapy targeting programmed-death 1 (PD-1) and its ligand PD-L1 can effectively prevent tumor immune escaping, and has been recognized with remarkable clinical benefits on cancer. Currently, antibody drugs take effect by blocking the target on the cell membrane. However, antibody drugs still face challenges in the aspect of deep penetration, multivalent recognition and chemical synthesis. Rationally designed targeting peptides is the befitting units for construction of the ‘nano antibody’. We first report herein a new peptide-AIE (aggregation-induced emission) hybrid supramolecular TPDP, which can specifically bind PD-L1 in vivo and in vitro with nanomolar affinity. It can be triggered by PD-L1 into ordered-aggregation ‘nano-spiderwebs’ and compactly cocoon the lesion surface and block PD-1/PD-L1 interaction on both membrane and cytoplasm in a dynamic manner, showing competitive effect over antibodies. It showed excellent in vivo tumor therapy effect in patient derived xenograft mice (PDX). What’s more, PD-L1 targeted antibody drugs take effect by blocking PD-L1 on the cell membrane, but intracellular PD-L1 are hard to be affect and like to be relocated on the membrane, which decreases the therapeutic benefits. In this study, the nano-spiderwebs could penetrate deeply into the cytoplasm and down-regulate the endogenous PD-L1 expression of the host, which could reduce the feedback of intracellular storage of PD-L1. We envision that this receptor-induced peptide ‘nano-spiderwebs’ will open an avenue for both blockade and inhibitor against PD-L1 and provide alternatives for targeting diagnostics and therapeutics towards this immune checkpoint.
HostingRepository	iProX
AnnounceDate	2020-08-15
AnnouncementXML	Submission_2020-08-14_18:59:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Minzhi Zhao
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	iTRAQ8plex reporter+balance reagent acylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-14 18:53:47	ID requested
⏵ 1	2020-08-14 18:59:04	announced

Dataset with its publication pending

submitter keyword: targeting peptide, receptor induced self-assembly, supramolecular, immune checkpoint blockade, PD-L1

Minzhi Zhao
contact affiliation	National Center for Nanoscience and Technology of China
contact email	zhaomz@nanoctr.cn
lab head
Minzhi Zhao
contact affiliation	National Center for Nanoscience and Technology of China
contact email	xgt1986627@163.com
dataset submitter

iProX dataset URI