{"doi":"10.1016/j.jbc.2022.101821","title":"Development and characterization of anti-galectin-9 antibodies that protect T cells from galectin-9-induced cell death","abstract":"Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two novel Gal-9-neutralizing antibodies that specifically react with the N-carbohydrate-recognition domain of human Gal-9 with high affinity. We also show using cell-based functional assays that these antibodies efficiently protected human T cells from Gal-9-induced cell death. Notably, in a T-cell/tumor cell coculture assay of cytotoxicity, these antibodies significantly promoted T cell-mediated killing of tumor cells. Taken together, our findings demonstrate potent inhibition of human Gal-9 by neutralizing antibodies, which may open new avenues for cancer immunotherapy.","journal":"Journal of Biological Chemistry","year":2022,"id":242261,"datarank":1.1452450645090595,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.5957108175896125,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.5957108175896125,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":33,"citers_with_citation_signal":26,"citers_with_endowment":26,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":251982,"name":"Linlin Sun","orcid":"0000-0003-0903-6571","position":1,"is_corresponding":false},{"id":872610,"name":"Ching-Fei Li","orcid":"0000-0001-7844-7003","position":2,"is_corresponding":false},{"id":872611,"name":"Yuhan Wang","orcid":"0000-0001-9422-3835","position":3,"is_corresponding":false},{"id":107243,"name":"Weiya Xia","orcid":null,"position":4,"is_corresponding":false},{"id":872612,"name":"Boning Liu","orcid":"0000-0002-3014-6049","position":5,"is_corresponding":false},{"id":866504,"name":"Yu‐Yi Chu","orcid":"0000-0003-3780-3061","position":6,"is_corresponding":false},{"id":872613,"name":"Laura Bover","orcid":"0000-0003-2566-464X","position":7,"is_corresponding":false},{"id":873286,"name":"Long Vien","orcid":null,"position":8,"is_corresponding":false},{"id":107263,"name":"Mien‐Chie Hung","orcid":"0000-0003-4317-4740","position":9,"is_corresponding":false},{"id":251984,"name":"Ri‐Yao Yang","orcid":"0000-0002-0278-4385","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:05.485568Z","pmid":"35283189","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":[]}