{"doi":"10.1002/ijc.35364","title":"Carbonic anhydrase‐9‐targeted near‐infrared photoimmunotherapy as a theranostic modality for clear cell renal cell carcinoma","abstract":"Carbonic anhydrase-9 (CA9) is highly expressed in clear cell renal cell carcinoma (ccRCC) cells despite no expression in normal kidney tissues. Thus, CA9 has been proposed as a theranostic target for radioligand therapy (RLT). However, ccRCC tends to be radioresistant and may not effectively respond to RLT. Alternatively, CA9 can be targeted for near-infrared photoimmunotherapy (NIR-PIT) of ccRCC. Here, we sought to test NIR-PIT using CA9 in a preclinical model of ccRCC to determine its potential as a therapeutic strategy. Tissue microarray analysis showed that membrane CA9 was expressed in the majority of ccRCC cases. In vitro, CA9-targeted NIR-PIT induced cell membrane damage and cell killing in all CA9-expressing ccRCC cell lines specifically, UOK154, UOK220, and UOK122. In vivo, CA9-targeted NIR-PIT significantly inhibited tumor growth and prolonged survival in UOK154 and UOK220 subcutaneous xenograft models. Notably, 70%-80% of mice achieved complete remission after a single treatment of NIR-PIT. Additionally, remaining tumors after the first NIR-PIT persistently expressed CA9, suggesting that remaining tumors can be treated with repeated NIR-PIT. Furthermore, CA9-targeted NIR-PIT induced significant cytoplasmic damages on ccRCC cells in UOK154 orthotopic xenograft models. In conclusion, CA9-targeted NIR-PIT, which allow for safe and repeated application on the same lesion, is a promising treatment for ccRCC, especially in the management of multiple primary ccRCC (e.g., von Hippel-Lindau syndrome) and oligometastatic ccRCC.","journal":"International Journal of Cancer","year":2025,"id":522713,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"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":896227,"name":"Seiichiro Takao","orcid":"0000-0002-7920-0763","position":1,"is_corresponding":false},{"id":262825,"name":"Aki Furusawa","orcid":"0000-0002-1339-4219","position":2,"is_corresponding":false},{"id":516923,"name":"Motofumi Suzuki","orcid":null,"position":3,"is_corresponding":false},{"id":378047,"name":"Youfeng Yang","orcid":"0009-0009-4808-6644","position":4,"is_corresponding":false},{"id":1250407,"name":"C. Ricketts","orcid":null,"position":5,"is_corresponding":false},{"id":1074650,"name":"Makoto Kano","orcid":"0009-0004-7659-1238","position":6,"is_corresponding":false},{"id":691990,"name":"Shuhei Okuyama","orcid":"0000-0001-7626-0560","position":7,"is_corresponding":false},{"id":1260315,"name":"Hiroshi Yamamoto","orcid":"0000-0001-8907-3166","position":8,"is_corresponding":false},{"id":1260814,"name":"Miyu Kano","orcid":null,"position":9,"is_corresponding":false},{"id":344240,"name":"Mark W. Ball","orcid":"0000-0003-1780-2627","position":10,"is_corresponding":false},{"id":110328,"name":"Peter L. Choyke","orcid":"0000-0003-1086-8826","position":11,"is_corresponding":false},{"id":51073,"name":"W. Marston Linehan","orcid":"0000-0001-7983-3109","position":12,"is_corresponding":false},{"id":262824,"name":"Hisataka Kobayashi","orcid":"0000-0003-1019-4112","position":13,"is_corresponding":false},{"id":691991,"name":"Hiroshi Fukushima","orcid":"0000-0001-7548-1580","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:49:58.707747Z","pmid":"39936451","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":[]}