PXD077619-1

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

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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