{"doi":"10.3389/fimmu.2023.1085547","title":"IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma","abstract":"Chimeric antigen receptor (CAR) T cell therapy in glioblastoma faces many challenges including insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, preclinical studies evaluating CAR T cells in glioblastoma focus on tumor models that express a single antigen, use immunocompromised animals, and/or pre-treat with lymphodepleting agents. While lymphodepletion enhances CAR T cell efficacy, it diminishes the endogenous immune system that has the potential for tumor eradication. Here, we engineered CAR T cells to express IL7 and/or Flt3L in 50% EGFRvIII-positive and -negative orthotopic tumors pre-conditioned with non-lymphodepleting irradiation. IL7 and IL7 Flt3L CAR T cells increased intratumoral CAR T cell abundance seven days after treatment. IL7 co-expression with Flt3L modestly increased conventional dendritic cells as well as the CD103+XCR1+ population known to have migratory and antigen cross-presenting capabilities. Treatment with IL7 or IL7 Flt3L CAR T cells improved overall survival to 67% and 50%, respectively, compared to 9% survival with conventional or Flt3L CAR T cells. We concluded that CAR T cells modified to express IL7 enhanced CAR T cell abundance and improved overall survival in EGFRvIII heterogeneous tumors pre-conditioned with non-lymphodepleting irradiation. Potentially IL7 or IL7 Flt3L CAR T cells can provide new opportunities to combine CAR T cells with other immunotherapies for the treatment of glioblastoma.","journal":"Frontiers in Immunology","year":2023,"id":322631,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":324733,"name":"Nalini Mehta","orcid":null,"position":1,"is_corresponding":false},{"id":302343,"name":"Ekaterina Ilich","orcid":"0000-0001-9807-3766","position":2,"is_corresponding":false},{"id":1036788,"name":"Steven H. Shen","orcid":"0000-0001-7635-9368","position":3,"is_corresponding":false},{"id":621416,"name":"Daniel Wilkinson","orcid":"0000-0001-9619-6914","position":4,"is_corresponding":false},{"id":384652,"name":"Alexa R. Anderson","orcid":"0000-0002-8566-4310","position":5,"is_corresponding":false},{"id":227278,"name":"Tatiana Segura","orcid":"0000-0003-1569-8686","position":6,"is_corresponding":false},{"id":496877,"name":"Luis Sánchez-Pérez","orcid":null,"position":7,"is_corresponding":false},{"id":268105,"name":"John H. Sampson","orcid":"0000-0002-0104-7658","position":8,"is_corresponding":false},{"id":320919,"name":"Ravi V. Bellamkonda","orcid":"0000-0003-0879-0767","position":9,"is_corresponding":false},{"id":1036787,"name":"Sheridan L. Swan","orcid":"0000-0002-0668-2386","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-19T01:07:47.432636Z","pmid":"36817432","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":[]}