PXD077619

PXD077619 is an original dataset announced via ProteomeXchange.

Title	Fc-optimized GITR antibody enhances a CD4 T cell-dendritic cell crosstalk to promote anti-tumor immunity
Description	Targeting the stimulatory immune checkpoint glucocorticoid-induced TNFR-related protein (GITR) using agonistic monoclonal antibodies (mAbs) is a promising strategy for cancer immunotherapy that activates effector T cells and eliminates regulatory T cells (Treg). The pre-clinical anti-tumor activity of GITR mAbs depends on activating Fcγ receptors (FcγRs). However, the human Fc-FcgR interactions in the activity of GITR mAbs have not been comprehensively investigated. To this end, we employed Fc protein and glycan engineering to modify the FcγR interactions of anti-GITR human mAbs and characterized them in humanized FcgR mice. We identified an Fc-optimized human IgG scaffold that enhances anti-tumor efficacy through multiple FcgR-mediated mechanisms, including Treg depletion and mutual engagement and activation of CD4+ T cells and dendritic cells, leading to anti-tumor cytotoxicity of CD4+ T cells and enhanced CD8+ T cell activity. Our findings suggest a strategy to optimize human GITR mAbs, harnessing beneficial immune pathways to improve their therapeutic potential.
HostingRepository	PRIDE
AnnounceDate	2026-05-13
AnnouncementXML	Submission_2026-05-13_08:48:59.717.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD077619
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yishai Levin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-26 08:15:42	ID requested
⏵ 1	2026-05-13 08:49:00	announced

10.6019/PXD077619;

submitter keyword: glycosylation, glycoproteomics,Tumor, immunity

Rony Dahan
contact affiliation	Department of Immunology, Weizmann Institute of Science
contact email	rony.dahan@weizmann.ac.il
lab head
Yishai Levin
contact affiliation	Weizmann Institute of Science, Israel
contact email	yishai.levin@gmail.com
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/2026/05/PXD077619

PRIDE project URI

• PRIDE
  1. PXD077619
     1. Label: PRIDE project
     2. Name: Fc-optimized GITR antibody enhances a CD4 T cell-dendritic cell crosstalk to promote anti-tumor immunity