PXD055544

PXD055544 is an original dataset announced via ProteomeXchange.

Title	Recurrent immunogenic neoantigens and their cognate T-cell receptors in treatment-resistant metastatic prostate cancer
Description	New approaches that generate long-lasting therapeutic responses in therapy-resistant metastatic cancer patients are urgently needed. To address this challenge, we developed SpotNeoMet, a novel data-driven pipeline that systematically identifies recurrently presented neopeptides in treatment-resistant patients. We identified seven therapy resistance mutations predicted to produce neo-peptides presented by common HLAs. Using HLA-immunopeptidomics, we discovered three novel neopeptides derived from Androgen Receptor (AR) H875Y, a common metastatic castration-resistant prostate cancer (mCRPC) mutation. We validated these neoantigens as highly immunogenic and then isolated and characterized cognate T-cell receptors (TCRs) from healthy donor peripheral blood mononuclear cells. We demonstrated that AR H875Y specific TCRs are highly specific and kill prostate cancer cells presenting AR neo-peptides in vitro and in vivo. Our new pipeline identifies novel immunotherapy targets and potential treatment options for mCRPC patients. Moreover, SpotNeoMet offers a systematic route to identify 'HLA-peptide' pairs and their cognate TCRs across treatment-resistant cancers.
HostingRepository	PRIDE
AnnounceDate	2025-10-20
AnnouncementXML	Submission_2025-10-20_02:01:13.441.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nofar Gumpert
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos; timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-04 07:09:14	ID requested
1	2025-10-03 05:08:18	announced
⏵ 2	2025-10-20 02:01:14	announced	2025-10-20: Updated project metadata.

Gumpert N, Sagie S, Arnedo-Pac C, Babu T, Weller C, Gonzalez-Perez A, Wang Y, Michel Tod, ó L, Levy R, Chen X, Greenberg P, Dayan-Rubinov M, Yakubovich E, Wasserman-Bartov T, Zerbib M, Gong J, Rebernick RJ, Oliveira Tercero A, Agundez Muriel L, Benedek G, Kedmi M, Oren R, Ben-Dor S, Levin Y, Troyanskaya OG, Munzur AD, Wyatt AW, Cieslik MP, Quigley DA, Van Allen EM, Anandasabapathy N, Mateo J, Yang X, Mart, í, nez-Jim, é, nez F, Lopez-Bigas N, Samuels Y, Recurrent immunogenic neoantigens and their cognate T-cell receptors in treatment-resistant metastatic prostate cancer. Cancer Discov, ():(2025) [pubmed]

10.1158/2159-8290.cd-24-1213;

submitter keyword: Treatment resistance, T cell receptor,Neopeptide

Yardena Samuels
contact affiliation	Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
contact email	yardena.samuels@weizmann.ac.il
lab head
Nofar Gumpert
contact affiliation	Weizmann Institute of Science
contact email	nofar.amsalem@weizmann.ac.il
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/2025/10/PXD055544

PRIDE project URI

• PRIDE
  1. PXD055544
     1. Label: PRIDE project
     2. Name: Recurrent immunogenic neoantigens and their cognate T-cell receptors in treatment-resistant metastatic prostate cancer