PXD054804

PXD054804 is an original dataset announced via ProteomeXchange.

Title	TCR-engineered T-cells directed against Ropporin-1 constitute a safe and effective treatment for triple-negative breast cancer in near-clinical models
Description	Triple-negative breast cancer (TNBC) shows an urgent need for new therapies. We discovered Ropporin 1 (ROPN1) as a target to treat TNBC with T-cells. ROPN1 showed high and homogenous expression in 90% of primary and metastatic TNBC but not in healthy tissues. HLA-A2-binding peptides were detected via immunopeptidomics and predictions and used to retrieve T-cell receptors (TCRs) from naïve repertoires. Following gene introduction into T-cells and stringent selection, we retrieved a highly specific TCR directed against the epitope FLYTYIAKV that did not recognize non-cognate epitopes from alternative source proteins. Notably, this TCR mediated killing of three-dimensional tumoroids in vitro and tumor cells in vivo and outperformed standard-of-care drugs. Finally, the T-cell product expressing this TCR and manufactured using a clinical protocol fulfilled standard safety and efficacy assays. Collectively, we have identified and preclinically validated ROPN1 as a target and anti-ROPN1 TCR T-cells as a treatment for the vast majority of TNBC patients.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_00:01:27.989.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-12 02:33:06	ID requested
⏵ 1	2025-05-07 00:01:28	announced

10.1158/2159-8290.cd-24-0168;

Kortleve D, Hammerl D, van Brakel M, Wijers R, Roelofs D, Kroese K, Timmermans MM, Liao CY, Huang S, Trapman-Jansen A, Foekens R, Michaux J, de Beijer MTA, Buschow SI, Demmers JAA, Kok M, Danen EHJ, Bassani-Sternberg M, Martens JWM, Abbott RJM, Debets R, TCR-Engineered T Cells Directed against Ropporin-1 Constitute a Safe and Effective Treatment for Triple-Negative Breast Cancer. Cancer Discov, 14(12):2450-2470(2024) [pubmed]

submitter keyword: adoptive T-cell therapy

cross-reactivity

epitopes

gene-engineering

immunopeptidomics

ropporin-1

T-cell receptor

triple negative breast cancer

tumor-restricted antigen

Jeroen Demmers
contact affiliation	Erasmus MC
contact email	j.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD054804

PRIDE project URI

• PRIDE
  1. PXD054804
     1. Label: PRIDE project
     2. Name: TCR-engineered T-cells directed against Ropporin-1 constitute a safe and effective treatment for triple-negative breast cancer in near-clinical models