{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328715/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328715"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Cell autonomous control of CAR signaling and receptor shedding via ADAM17-mediated proteolysis","description":"We sought to endow T cell autonomous regulation of cell surface protein expression by exploiting the conditional proteolytic activity of ADAM17 following T cell activation. Screening of canonical ADAM17 substrates yielded a minimal 15-aa CD62L-derived motif that confers rapid and reversible cleavage of a receptor following T cell activation—termed Activation-Induced Release (AIR). Embedding AIR into tonic-signaling CARs reduced basal CAR expression proportional to the degree of tonic signaling induced, curtailing exhaustion and improving antitumor potency. In non-tonic signaling CARs, AIR decreased activation-induced cell death and enhanced T cell expansion after stimulation. AIR’s modularity supports higher-order logic-gating; AIR-regulated peptide masks enable antigen-dependent unmasking of an EGFR-targeting CAR. Finally, CRISPR knock-in of AIR into endogenous FAS or TGFBR2 endowed them with activation-induced shedding, which enhanced tumor clearance, while preserving signaling in non-activating conditions. AIR is a compact switch that provides fast, autonomous regulation of surface proteins for next-generation cell therapies.","dates":{"publication":"2026/04/26"},"accession":"GSE328715","cross_references":{"GSM":["GSM9688120","GSM9688100","GSM9688121","GSM9688102","GSM9688101","GSM9688104","GSM9688103","GSM9688106","GSM9688105","GSM9688108","GSM9688107","GSM9688109","GSM9688098","GSM9688097","GSM9688111","GSM9688110","GSM9688099","GSM9688113","GSM9688112","GSM9688115","GSM9688114","GSM9688117","GSM9688116","GSM9688119","GSM9688118"],"GPL":["34284"],"GSE":["328715"],"taxon":["Homo sapiens"]}}