{"doi":"10.1053/j.seminhematol.2024.07.003","title":"Tuning CAR T-cell therapies for efficacy and reduced toxicity","abstract":null,"journal":"Seminars in Hematology","year":2024,"id":622537,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1608572,"name":"Patricia Rubio-Reyes","orcid":null,"position":1,"is_corresponding":false},{"id":1353437,"name":"Rachel Perret","orcid":"0000-0003-1225-5097","position":2,"is_corresponding":false},{"id":1608573,"name":"Robert Weinkove","orcid":null,"position":3,"is_corresponding":false},{"id":1608571,"name":"Danielle Blud","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Tuning CAR T-cell therapies for efficacy and reduced toxicity","abstract":"Chimeric antigen receptor (CAR) T-cell therapies are a standard of care for certain relapsed or refractory B-cell cancers. However, many patients do not respond to CAR T-cell therapy or relapse later, short- and long-term toxicities are common, and current CAR T-cell therapies have limited efficacy for solid cancers. The gene engineering inherent in CAR T-cell manufacture offers an unprecedented opportunity to control cellular characteristics and design products that may overcome these limitations. This review summarises available methods to \"tune\" CAR T-cells for optimal efficacy and safety. The components of a typical CAR, and the modifications that can influence CAR T-cell function are discussed. Methods of engineering passive, inducible or autonomous control mechanisms into CAR T-cells, allowing selective limitation or enhancement of CAR T-cell activity are reviewed. The impact of manufacturing processes on CAR T-cell function are considered, including methods of limiting CAR T-cell terminal differentiation and exhaustion, and the use of specific T-cell subsets as the CAR T starting material. We discuss the use of multicistronic transgenes and multiplexed gene editing. Finally, we highlight the need for innovative clinical trial designs if we are to make the most of the opportunities offered by CAR T-cell therapies.","is_dataset_classified":null,"base_score":2.639057329615259,"endowment":2.639057329615259,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39095226","pmcid":null,"openalex_id":"https://openalex.org/W4400381275","authors":[],"funders":[],"total_grants":0,"fwci":2.343,"citation_percentile":0.90908967,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2025,"count":6},{"year":2026,"count":5}],"oa_status":"closed","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0037196324000829?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0037196324000829?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1053/j.seminhematol.2024.07.003","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39095226","host_type":"repository"}],"fields_of_study":["CAR-T cell therapy research","Viral Infectious Diseases and Gene Expression in Insects","Nanowire Synthesis and Applications","Humans","Immunotherapy, Adoptive","Receptors, Chimeric Antigen","T-Lymphocytes","Neoplasms","Gene Editing","Receptors, Antigen, T-Cell"],"mesh_terms":["Gene Editing","Receptors, Chimeric Antigen","Humans","Neoplasms","Receptors, Antigen, T-Cell","T-Lymphocytes","Immunotherapy, Adoptive"],"keywords":["Chimeric antigen receptor","Cell therapy","T cell","Genetic enhancement","Immunotherapy","CAR T-cell therapy","Cell","Medicine","Cancer research","Immunology","Biology","Immune system","Gene","Genetic engineering","Adverse drug reaction","Treatment Efficacy","single-chain variable fragments","Chimeric Antigen Receptors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T20:00:36.494716Z","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":[]}