{"doi":"10.1016/j.omton.2025.200957","title":"CD147-CAR-NK cell therapy shows minimal toxicities in human CD147 transgenic mouse model with solid tumors","abstract":"The toxicity of chimeric antigen receptor-natural killer (CAR-NK) therapy has not been tested in solid tumors, compared with CAR-T therapy side by side. To address this, we investigated the CD147-CAR-NK \"on-target/off-tumor\" toxicity and neurotoxicity in human CD147-transgenic (hCD147TG) mice with hepatocellular carcinoma (HCC). We first tested the in vitro cytotoxicity of CD147-CAR-NK against CD147 + tumor and CD147 + healthy cells. Both CD147-CAR-NK cells and CD147-IL15-CAR-NK (autocrine expressing interleukin [IL]-15) can kill tumor cells specifically but not CD147 + healthy lung and spleen tissue from hCD147TG mice. In vivo assays show minimal systemic toxicities against CD147 + healthy tissues but 1-week-longer persistence times in tumor than non-tumor tissues. To evaluate neurotoxicity, we compared the expression of ionized calcium-binding adaptor protein 1 (IBA1), glial fibrillary acidic protein (GFAP), and inducible nitric oxide synthase (iNOS) between CD147-CAR-T- and CD147-CAR-NK-treated hCD147TG mice with HCC. Both CD147-CAR-T- and CD147-CAR-NK-treated mice exhibited higher GFAP and IBA1 expression than control groups. CD147-CAR-T-treated mice showed an increase in iNOS compared to the control groups. The behavioral studies testing spatial memory showed that mice treated with CD147-CAR-NK exhibit better memory function than CD147-CAR-T-treated mice. This study provides a deeper understanding of the CD147-CAR-NK systemic toxicities and neurotoxicity of CD147-CAR-NK relative to CD147-CAR-T therapy.","journal":"Molecular Therapy Oncology","year":2025,"id":513220,"datarank":0.406814211839033,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.047129920919277306,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.047129920919277306,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":10,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9647,"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":1374267,"name":"Sang Hoon Kim","orcid":"0000-0002-0575-953X","position":1,"is_corresponding":false},{"id":244929,"name":"Tseng Hsiang-Chi","orcid":"0000-0001-7745-413X","position":2,"is_corresponding":false},{"id":1237408,"name":"Maeve Elizabeth Byrne","orcid":null,"position":3,"is_corresponding":false},{"id":582646,"name":"Wei-Chung Tsao","orcid":"0000-0002-4801-7333","position":4,"is_corresponding":false},{"id":1374268,"name":"Sang Hoon Lee","orcid":"0000-0002-7146-3702","position":5,"is_corresponding":false},{"id":1065510,"name":"Zhongren Zhou","orcid":"0000-0002-6977-8414","position":6,"is_corresponding":false},{"id":1183637,"name":"Mi-Hyeon Jang","orcid":null,"position":7,"is_corresponding":false},{"id":244938,"name":"Dongfang Liu","orcid":"0000-0002-7295-8088","position":8,"is_corresponding":false},{"id":1234128,"name":"Youssef Sabha","orcid":"0009-0006-2823-7853","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:17.908238Z","pmid":"40160933","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":[]}