{"doi":"10.3390/cells13090726","title":"A Roadmap of CAR-T-Cell Therapy in Glioblastoma: Challenges and Future Perspectives","abstract":"Glioblastoma (GBM) is the most common primary malignant brain tumor, with a median overall survival of less than 2 years and a nearly 100% mortality rate under standard therapy that consists of surgery followed by combined radiochemotherapy. Therefore, new therapeutic strategies are urgently needed. The success of chimeric antigen receptor (CAR) T cells in hematological cancers has prompted preclinical and clinical investigations into CAR-T-cell treatment for GBM. However, recent trials have not demonstrated any major success. Here, we delineate existing challenges impeding the effectiveness of CAR-T-cell therapy for GBM, encompassing the cold (immunosuppressive) microenvironment, tumor heterogeneity, T-cell exhaustion, local and systemic immunosuppression, and the immune privilege inherent to the central nervous system (CNS) parenchyma. Additionally, we deliberate on the progress made in developing next-generation CAR-T cells and novel innovative approaches, such as low-intensity pulsed focused ultrasound, aimed at surmounting current roadblocks in GBM CAR-T-cell therapy.","journal":"Cells","year":2024,"id":420239,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1044107,"name":"Marco Gallus","orcid":"0009-0007-4954-8420","position":1,"is_corresponding":false},{"id":685164,"name":"Su Phyu","orcid":"0000-0003-1775-6966","position":2,"is_corresponding":false},{"id":1203365,"name":"Jeffrey Haegelin","orcid":null,"position":3,"is_corresponding":false},{"id":238094,"name":"John de Groot","orcid":"0000-0003-1454-6461","position":4,"is_corresponding":false},{"id":271186,"name":"Hideho Okada","orcid":"0000-0003-0076-9920","position":5,"is_corresponding":false},{"id":368971,"name":"Megan Montoya","orcid":"0000-0002-9465-3146","position":0,"is_corresponding":true}],"reference_count":207,"raw_metadata":null,"created_at":"2026-07-19T01:57:25.777459Z","pmid":"38727262","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":[]}