{"doi":"10.1093/neuonc/noab182","title":"Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice","abstract":"BACKGROUND: Rigorous preclinical studies of chimeric antigen receptor (CAR) immunotherapy will require large quantities of consistent and high-quality CAR-transduced T (CART) cells that can be used in syngeneic mouse glioblastoma (GBM) models. To this end, we developed a novel transgenic (Tg) mouse strain with a fully murinized CAR targeting epidermal growth factor receptor variant III (EGFRvIII). METHODS: We first established the murinized version of EGFRvIII-CAR and validated its function using a retroviral vector (RV) in C57BL/6J mice bearing syngeneic SB28 GBM expressing EGFRvIII. Next, we created C57BL/6J-background Tg mice carrying the anti-EGFRvIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. We bred these mice with CD4-Cre Tg mice to allow CAR expression on T cells and evaluated the function of the CART cells both in vitro and in vivo. To inhibit immunosuppressive myeloid cells within SB28 GBM, we also evaluated a combination approach of CART and an anti-EP4 compound (ONO-AE3-208). RESULTS: Both RV- and Tg-CART cells demonstrated specific cytotoxic activities against SB28-EGFRvIII cells. A single intravenous infusion of EGFRvIII-CART cells prolonged the survival of glioma-bearing mice when preceded by a lymphodepletion regimen with recurrent tumors displaying profound EGFRvIII loss. The addition of ONO-AE3-208 resulted in long-term survival in a fraction of CART-treated mice and those survivors demonstrated delayed growth of subcutaneously re-challenged both EGFRvIII+ and parental EGFRvIII- SB28. CONCLUSION: Our new syngeneic CAR Tg mouse model can serve as a useful tool to address clinically relevant questions and develop future immunotherapeutic strategies.","journal":"Neuro-Oncology","year":2021,"id":187933,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9261,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":594393,"name":"Yafei Hou","orcid":null,"position":1,"is_corresponding":false},{"id":748932,"name":"Ryosuke Naka","orcid":null,"position":2,"is_corresponding":false},{"id":748177,"name":"Akane Yamamichi","orcid":"0000-0002-8141-7339","position":3,"is_corresponding":false},{"id":615212,"name":"Tiffany Chen","orcid":"0000-0003-2546-2941","position":4,"is_corresponding":false},{"id":617184,"name":"Yitzhar Goretsky","orcid":null,"position":5,"is_corresponding":false},{"id":748178,"name":"Ryusuke Hatae","orcid":"0000-0001-5636-8064","position":6,"is_corresponding":false},{"id":271177,"name":"Takahide Nejo","orcid":"0000-0002-9191-8823","position":7,"is_corresponding":false},{"id":400563,"name":"Gary Kohanbash","orcid":"0000-0002-3953-8022","position":8,"is_corresponding":false},{"id":504250,"name":"Abigail Mende","orcid":"0000-0002-8893-7839","position":9,"is_corresponding":false},{"id":368971,"name":"Megan Montoya","orcid":"0000-0002-9465-3146","position":10,"is_corresponding":false},{"id":615941,"name":"Kira Downey","orcid":"0000-0001-7418-2239","position":11,"is_corresponding":false},{"id":748179,"name":"David Diebold","orcid":"0000-0002-6857-767X","position":12,"is_corresponding":false},{"id":748933,"name":"Jayne Skinner","orcid":null,"position":13,"is_corresponding":false},{"id":273671,"name":"Hong-Erh Liang","orcid":"0000-0003-0620-7224","position":14,"is_corresponding":false},{"id":694956,"name":"Bjoern Schwer","orcid":"0000-0003-4367-6265","position":15,"is_corresponding":false},{"id":271186,"name":"Hideho Okada","orcid":"0000-0003-0076-9920","position":16,"is_corresponding":false},{"id":634193,"name":"Pavlina Chuntova","orcid":"0000-0002-5356-9909","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:49:05.976005Z","pmid":"34347086","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":[]}