{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325953/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325953"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"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 involves increased effector T cell activity and regulatory T cell (Treg) elimination. The pre-clinical anti-tumor activity of GITR mAbs depends on activating Fcγ receptors (FcγRs). However, the role of human Fc-FcγR interactions in the activity of GITR mAbs has not been comprehensively addressed. 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 FcγR mice. We identified an Fc-optimized human IgG scaffold that increased binding to activating FcγRIIa and FcγRIIIa, enhancing anti-tumor efficacy. This Fc-optimized activity was mediated by multiple mechanisms that are unique to GITR mAb, including FcγR-mediated Treg depletion and mutual engagement and activation of CD4+ T cells and dendritic cells, leading to anti-tumor cytotoxic activity 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.","dates":{"publication":"2026/05/12"},"accession":"GSE325953","cross_references":{"GSM":["GSM9617712","GSM9617713"],"GPL":["24247"],"GSE":["325953"],"taxon":["Mus musculus"]}}