{"doi":"10.17615/w9bt-7179","title":"Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy","abstract":"Despite over 20 years of clinical use, IL-2 has not fulfilled expectations as a safe and effective form of tumour immunotherapy. Expression of the high affinity IL-2Rα chain on regulatory T cells mitigates the anti-tumour immune response and its expression on vascular endothelium is responsible for life threatening complications such as diffuse capillary leak and pulmonary oedema. Here we describe the development of a recombinant fusion protein comprised of a cowpox virus encoded NKG2D binding protein (OMCP) and a mutated form of IL-2 with poor affinity for IL-2Rα. This fusion protein (OMCP-mutIL-2) potently and selectively activates IL-2 signalling only on NKG2D-bearing cells, such as natural killer (NK) cells, without broadly activating IL-2Rα-bearing cells. OMCP-mutIL-2 provides superior tumour control in several mouse models of malignancy and is not limited by mouse strain-specific variability of NK function. In addition, OMCP-mutIL-2 lacks the toxicity and vascular complications associated with parental wild-type IL-2.","journal":"UNC Libraries","year":2020,"id":142467,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230331,"name":"Andrew E. Gelman","orcid":"0000-0002-0711-6343","position":1,"is_corresponding":false},{"id":377582,"name":"Ryuji Higashikubo","orcid":null,"position":2,"is_corresponding":false},{"id":267156,"name":"Alexander S. Krupnick","orcid":"0000-0002-1790-6197","position":3,"is_corresponding":false},{"id":225534,"name":"Daved H. Fremont","orcid":"0000-0002-8544-2689","position":4,"is_corresponding":false},{"id":609629,"name":"Reza Ghasemi","orcid":null,"position":5,"is_corresponding":false},{"id":273856,"name":"Daniel Kreisel","orcid":"0000-0002-7711-8651","position":6,"is_corresponding":false},{"id":608979,"name":"Saeed Arefanian","orcid":"0000-0002-3073-0907","position":7,"is_corresponding":false},{"id":607030,"name":"Xiaoli Wang","orcid":"0000-0003-3136-9807","position":8,"is_corresponding":false},{"id":608980,"name":"Eric Lazear","orcid":"0000-0001-6173-8904","position":9,"is_corresponding":false},{"id":374214,"name":"Alexander Zheleznyak","orcid":"0000-0002-1054-3768","position":10,"is_corresponding":false},{"id":226359,"name":"Beatriz M. Carreno","orcid":"0000-0002-8123-2035","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:31.424593Z","pmid":null,"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":[]}