{"doi":"10.1101/2022.02.16.480729","title":"Antigen-dependent inducible T cell reporter system for PET imaging of breast cancer and glioblastoma","abstract":"Abstract For the past several decades, chimeric antigen receptor T cell (CAR T) therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo . Using synthetic biology, we engineered T cells with a chimeric receptor SyNthetic Intramembrane Proteolysis Receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette upon recognition of specific tumor markers. We then applied a SNIPR-based positron emission tomography (PET) reporter system to two cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors respectively. Antigen-specific reporter induction of the SNIPR-PET T cells was confirmed in vitro using GFP fluorescence, luciferase luminescence, and the HSV-TK PET reporter with [ 18 F]FHBG. T cells associated with their target antigens were successfully imaged using PET in dual xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII-animal models, with > 10-fold higher [ 18 F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. The main innovation described is therefore PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302688,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":587376,"name":"Matthew F.L. Parker","orcid":null,"position":1,"is_corresponding":false},{"id":806753,"name":"Iowis Zhu","orcid":"0000-0001-7852-0987","position":2,"is_corresponding":false},{"id":940613,"name":"Aryn A. Alanizi","orcid":null,"position":3,"is_corresponding":false},{"id":940129,"name":"Carlos I. Rodríguez","orcid":"0000-0002-4325-6132","position":4,"is_corresponding":false},{"id":806754,"name":"Raymond Liu","orcid":"0000-0002-4667-9632","position":5,"is_corresponding":false},{"id":271182,"name":"Payal Watchmaker","orcid":"0000-0002-0944-3890","position":6,"is_corresponding":false},{"id":378877,"name":"Mausam Kalita","orcid":"0000-0002-4847-2678","position":7,"is_corresponding":false},{"id":538163,"name":"Joseph Blecha","orcid":null,"position":8,"is_corresponding":false},{"id":339305,"name":"Justin Luu","orcid":"0009-0005-3562-7529","position":9,"is_corresponding":false},{"id":940130,"name":"Brian Wright","orcid":"0000-0002-7836-8273","position":10,"is_corresponding":false},{"id":364750,"name":"Suzanne E. Lapi","orcid":"0000-0003-0090-0191","position":11,"is_corresponding":false},{"id":272317,"name":"Robert R. Flavell","orcid":"0000-0002-8694-1199","position":12,"is_corresponding":false},{"id":271186,"name":"Hideho Okada","orcid":"0000-0003-0076-9920","position":13,"is_corresponding":false},{"id":81156,"name":"Thea D. Tlsty","orcid":"0000-0003-0903-1631","position":14,"is_corresponding":false},{"id":249364,"name":"Kole T. Roybal","orcid":"0000-0003-3030-7954","position":15,"is_corresponding":false},{"id":488328,"name":"David M. Wilson","orcid":"0000-0002-1095-046X","position":16,"is_corresponding":false},{"id":994890,"name":"Jaehoon Shin","orcid":"0009-0000-5773-7546","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T00:32:20.348385Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}