{"doi":"10.1093/noajnl/vdaf074","title":"Comparative evaluation of CAR-expressing T-, NK-, NKT-cells, and macrophages in an immunocompetent mouse glioma model","abstract":"Background: While chimeric antigen receptor (CAR) T-cells are promising, there is a rapidly growing interest in developing other CAR-expressing immune cells. However, to date, no reported studies evaluated these cells side-by-side in immune-competent glioma models. Methods: We developed a novel C57BL/6-background transgenic mouse strain with all hematopoietic cells carrying the anti-epidermal growth factor receptor (EGFR)vIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. Crossing with mice transgenic for Vav-Cre allowed the expression of anti-EGFRvIII CAR in all hematopoietic cells. In particular, we evaluated CAR-T, CAR-NKT, CAR-NK-cells, and CAR-macrophages in a syngeneic mouse SB28EGFRVIII glioma model. Results: CAR-NK and CAR-NKT-cells demonstrated anti-tumor effects comparable to CAR-T cells in vitro. A single intratumoral administration of CAR-T and CAR-NKT cells in combination mediated superior therapeutic efficacy compared to CAR-T cells or CAR-NKT-cells alone. A single intravenous infusion of CAR-NK cells following lymphodepletion failed to mediate significant anti-glioma effects. Additionally, intratumoral injection of CAR-NK cells did not confer therapeutic benefit. Contrary to previous reports using human macrophages, CAR-macrophages did not demonstrate enhanced antigen-presentation activity against glioma cells compared to non-CAR macrophages. Intratumorally administered CAR-macrophages failed to demonstrate local persistence or anti-tumor effects in vivo. Conclusions: These data provide a valuable basis as to which immune cells can mediate effective anti-glioma response in an immuno-competent glioma environment. Our data also suggest that a combination of CAR-T and CAR-NKT-cells may represent a promising therapeutic strategy.","journal":"Neuro-Oncology Advances","year":2025,"id":518215,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271182,"name":"Payal Watchmaker","orcid":"0000-0002-0944-3890","position":1,"is_corresponding":false},{"id":748177,"name":"Akane Yamamichi","orcid":"0000-0002-8141-7339","position":2,"is_corresponding":false},{"id":1207165,"name":"Keith Kyewalabye","orcid":"0000-0003-3645-6328","position":3,"is_corresponding":false},{"id":272885,"name":"Kaori Okada","orcid":null,"position":4,"is_corresponding":false},{"id":685164,"name":"Su Phyu","orcid":"0000-0003-1775-6966","position":5,"is_corresponding":false},{"id":617184,"name":"Yitzhar Goretsky","orcid":null,"position":6,"is_corresponding":false},{"id":1203365,"name":"Jeffrey Haegelin","orcid":null,"position":7,"is_corresponding":false},{"id":915290,"name":"Psalm Pineo-Cavanaugh","orcid":"0000-0002-1521-1607","position":8,"is_corresponding":false},{"id":1044107,"name":"Marco Gallus","orcid":"0009-0007-4954-8420","position":9,"is_corresponding":false},{"id":1365687,"name":"Lan Phung","orcid":null,"position":10,"is_corresponding":false},{"id":615212,"name":"Tiffany Chen","orcid":"0000-0003-2546-2941","position":11,"is_corresponding":false},{"id":1386121,"name":"Haoyu Long","orcid":null,"position":12,"is_corresponding":false},{"id":634193,"name":"Pavlina Chuntova","orcid":"0000-0002-5356-9909","position":13,"is_corresponding":false},{"id":645834,"name":"David H. Raulet","orcid":"0000-0002-1257-8649","position":14,"is_corresponding":false},{"id":372492,"name":"Masaki Terabe","orcid":"0000-0002-1777-0189","position":15,"is_corresponding":false},{"id":271186,"name":"Hideho Okada","orcid":"0000-0003-0076-9920","position":16,"is_corresponding":false},{"id":748178,"name":"Ryusuke Hatae","orcid":"0000-0001-5636-8064","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:49:09.679930Z","pmid":"40376677","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":[]}