{"doi":"10.1007/s00262-024-03788-1","title":"Chimeric antigen receptor dendritic cells targeted delivery of a single tumoricidal factor for cancer immunotherapy","abstract":"Abstract Background Chimeric antigen receptor (CAR)-T cells have been used to treat blood cancers by producing a wide variety of cytokines. However, they are not effective in treating solid cancers and can cause severe side-effects, including cytokine release syndrome. TNF α is a tumoricidal cytokine, but it markedly increases the protein levels of cIAP1 and cIAP2, the members of inhibitor of apoptosis protein (IAP) family of E3 ubiquitin ligase that limits caspase-induced apoptosis. Degradation of IAP proteins by an IAP antagonist does not effectively kill cancer cells but enables TNF α to strongly induce cancer cell apoptosis. It would be a promising approach to treat cancers by targeted delivery of TNF α through an inactive adoptive cell in combination with an IAP antagonist. Methods Human dendritic cells (DCs) were engineered to express a single tumoricidal factor, TNF α , and a membrane-anchored Mucin1 antibody scFv, named Mucin 1 directed DCs expressing TNF α (M-DCs TNF ). The efficacy of M-DCs TNF in recognizing and treating breast cancer was tested in vitro and in vivo. Results Mucin1 was highly expressed on the surface of a wide range of human breast cancer cell lines. M-DCs TNF directly associated with MDA-MB-231 cells in the bone of NSG mice. M-DCs TNF plus an IAP antagonist, SM-164, but neither alone, markedly induce MDA-MB-231 breast cancer cell apoptosis, which was blocked by TNF antibody. Importantly, M-DCs TNF combined with SM-164, but not SM-164 alone, inhibited the growth of patient-derived breast cancer in NSG mice. Conclusion An adoptive cell targeting delivery of TNF α combined with an IAP antagonist is a novel effective approach to treat breast cancer and could be expanded to treat other solid cancers. Unlike CAR-T cell, this novel adoptive cell is not activated to produce a wide variety of cytokines, except for additional overexpressed TNF, and thus could avoid the severe side effects such as cytokine release syndrome.","journal":"Cancer Immunology Immunotherapy","year":2024,"id":427862,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"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":1228577,"name":"Philip Milton","orcid":"0000-0001-6465-8221","position":1,"is_corresponding":false},{"id":1228578,"name":"Chutamath Sittplangkoon","orcid":"0000-0002-9962-1899","position":2,"is_corresponding":false},{"id":369202,"name":"Xin Liu","orcid":"0009-0004-7970-2327","position":3,"is_corresponding":false},{"id":1229028,"name":"Zhining Sui","orcid":null,"position":4,"is_corresponding":false},{"id":226223,"name":"Brendan F. Boyce","orcid":"0000-0002-3587-4854","position":5,"is_corresponding":false},{"id":355644,"name":"Zhenqiang Yao","orcid":"0000-0002-4664-3648","position":6,"is_corresponding":false},{"id":370362,"name":"Rong Duan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:58:52.576447Z","pmid":"39105847","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":[]}