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PXD040651-1

PXD040651 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePRAME and CTCFL-reactive TCRs for the treatment of ovarian cancer
DescriptionRecurrent disease emerges in the majority of patients with ovarian cancer (OVCA). Adoptive T-cell therapies with T-cell receptors (TCRs) targeting tumor-associated antigens (TAAs) are considered promising solutions for less-immunogenic ‘cold’ ovarian tumors. In order to treat a broader patient population, more TCRs targeting peptides derived from different TAAs binding in various HLA class I molecules are essential. By performing a differential gene expression analysis using mRNA-seq datasets, PRAME, CTCFL and CLDN6 were selected as strictly tumor-specific TAAs, with high expression in ovarian cancer and at least 20-fold lower expression in all healthy tissues of risk. In primary OVCA patient samples and cell lines we confirmed expression and identified naturally expressed TAA-derived peptides in the HLA class I ligandome. Subsequently, high-avidity T-cell clones recognizing these peptides were isolated from the allo-HLA T-cell repertoire of healthy individuals. Three PRAME TCRs and one CTCFL TCR of the most promising T-cell clones were sequenced, and transferred to CD8+ T cells. The PRAME TCR-T cells demonstrated potent and specific antitumor reactivity in vitro and in vivo. The CTCFL TCR-T cells efficiently recognized primary patient-derived OVCA cells, and OVCA cell lines treated with demethylating agent 5-aza-2′-deoxycytidine (DAC). The identified PRAME and CTCFL TCRs are promising candidates for the treatment of patients with ovarian cancer, and are an essential addition to the currently used HLA-A*02:01 restricted PRAME TCRs. Our selection of differentially expressed genes, naturally expressed TAA peptides and potent TCRs can improve and broaden the use of T-cell therapies for patients with ovarian cancer or other PRAME or CTCFL expressing cancers.
HostingRepositoryPRIDE
AnnounceDate2023-03-11
AnnouncementXMLSubmission_2023-03-10_20:19:13.102.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRaymanTjokrodirijo
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-03-07 03:28:10ID requested
12023-03-10 20:19:13announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Ovarian cancer
PRAME
CTCFL
CLDN6
TCR gene transfer
T-cell therapy
immunotherapy
peptide
allogeneic HLA
Contact List
Peter A. vanVeelen
contact affiliationLeiden University Medical Center, Center for Proteomics and Metabolomics, PO Box 9600, Postal zone P1-Q, 2300 RC Leiden, The Netherlands
contact emailP.A.van_Veelen@lumc.nl
lab head
RaymanTjokrodirijo
contact affiliationLeiden University Medical Center, Proteomics group
contact emailR.T.N.Tjokrodirijo@lumc.nl
dataset submitter
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Dataset FTP location
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