{"doi":"10.1136/jitc-2025-013040","title":"Chimeric antigen receptor dendritic cells suppress melanoma growth in preclinical cancer models","abstract":"BACKGROUND: Chimeric antigen receptor (CAR)-T cell therapy has been successful for the treatment of hematological cancers but less effective against solid tumors, a phenomenon that results from the immunosuppressive nature of the tumor microenvironment. As a strategy to improve the treatment of solid tumors, we applied CAR therapy to dendritic cells (DCs) to generate CAR-DCs. The CAR targeted the human epidermal growth factor receptor 2 (HER2) which is overexpressed in breast cancer to defeat the immunosuppressive nature of the tumor microenvironment. METHODS: CAR-DCs were generated by lentiviral vector transduction of SAMHD1 knock-out murine bone marrow-derived DCs. The vectors coexpressed CD40L and a soluble form of programmed cell death 1 (PD-1), a checkpoint inhibitor. To increase the durability of CAR-DCs, a gene encoding the cytokine GM-CSF was introduced into the CAR vector. The CAR-DCs were injected into mice bearing B16.HER2 melanoma tumors. Tumor growth was measured, and T cell functionality was determined by IFNγ expression and in vitro cytolytic assay. RESULTS: CAR-DCs suppressed the growth of B16.HER2 tumors and induced the proliferation and activation of tumor-infiltrating cytolytic CD8+T cells. The PD-1 checkpoint inhibitor further augmented the antitumor response and prevented T cell exhaustion. Vectored expression of GM-CSF increased the durability of the antitumor response. CONCLUSIONS: CAR-DCs could be an effective strategy for therapies against solid tumors that should be further explored. The approach relies on the antigen-presenting ability of DCs and their role in T cell activation and can be coupled with checkpoint inhibition in place of monoclonal antibody treatment.","journal":"Journal for ImmunoTherapy of Cancer","year":2025,"id":549838,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"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":1445179,"name":"Wallace ZH Wong","orcid":null,"position":1,"is_corresponding":false},{"id":1445180,"name":"Benjamin S Russell","orcid":null,"position":2,"is_corresponding":false},{"id":1445181,"name":"Jose LM Semana","orcid":null,"position":3,"is_corresponding":false},{"id":465265,"name":"Ruofan Li","orcid":"0000-0001-7746-9569","position":4,"is_corresponding":false},{"id":16989,"name":"Nathaniel R. Landau","orcid":"0000-0002-9997-1004","position":5,"is_corresponding":false},{"id":16988,"name":"Takuya Tada","orcid":"0000-0003-0779-9954","position":6,"is_corresponding":false},{"id":1128515,"name":"Julia Minnee","orcid":"0009-0003-3340-9670","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:54:12.321988Z","pmid":"41475842","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":[]}