{"doi":"10.1101/2020.03.15.993063","title":"Sustained Release of IL-2 Using an Injectable Hydrogel Prevents Autoimmune Diabetes","abstract":"ABSTRACT Interleukin 2 (IL-2) is a promising therapy for autoimmune type 1 diabetes (T1D), but the short half-life in vivo (less than 6 minutes) limits effective tissue exposure to IL-2. Tissue exposure is required for the tolerogenic effects of IL-2. We have developed an injectable hydrogel that incorporates heparin polymers to enable the sustained release of IL-2. This platform uses clinical grade and commercially available materials, including collagen, hyaluronan, and heparin, to deliver IL-2 by slowly degrading and releasing IL-2 over a two-week period in vivo . We find that heparin potentiates the activity of IL-2 and IL-2-mediated expansion of Foxp3+ regulatory T cell (Treg). Hydrogel-mediated IL-2 release showed a reduction of CD4+ and CD8+ T cells and an increase of FoxP3+ Treg in the lymph nodes of injected mice. Moreover, in the Non-Obese Diabetic (NOD) mouse model of T1D once-weekly administration of IL-2 hydrogels prevented diabetes onset as efficiently as 3x weekly repeated injections of soluble IL-2. Together these data suggest that heparin-containing hydrogels may have benefit in delivering low-dose IL-2 and promoting immune tolerance in autoimmune diabetes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122639,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"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":0.9483,"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":381353,"name":"Gernot Kaber","orcid":"0000-0002-6184-5192","position":1,"is_corresponding":false},{"id":264000,"name":"Michael J. Kratochvil","orcid":"0000-0002-8845-2524","position":2,"is_corresponding":false},{"id":41008,"name":"Hedwich F. Kuipers","orcid":"0000-0002-7275-5889","position":3,"is_corresponding":false},{"id":422978,"name":"Shannon M. Ruppert","orcid":null,"position":4,"is_corresponding":false},{"id":381359,"name":"Koshika Yadava","orcid":"0000-0002-5827-9177","position":5,"is_corresponding":false},{"id":421756,"name":"Jason Yang","orcid":"0000-0001-6576-3023","position":6,"is_corresponding":false},{"id":262482,"name":"Sarah C. Heilshorn","orcid":"0000-0002-9801-6304","position":7,"is_corresponding":false},{"id":308289,"name":"S. Alice Long","orcid":"0000-0002-0281-1240","position":8,"is_corresponding":false},{"id":251269,"name":"Alberto Pugliese","orcid":"0000-0002-7211-0319","position":9,"is_corresponding":false},{"id":239766,"name":"Paul L. Bollyky","orcid":"0000-0003-2499-9448","position":10,"is_corresponding":false},{"id":381352,"name":"Nadine Nagy","orcid":"0000-0002-2638-2436","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:55.385653Z","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":[]}